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Addressing barriers to perinatal care: a case study of the Access to Maternity Care Committee in Washington State.

Access to obstetrical services has deteriorated in recent years, as large numbers of physicians have discontinued or restricted obstetrical practice. In Washington State, one response to this access crisis has been the establishment of the Access to Maternity Care Committee (AMCC), an ad hoc group composed primarily of private sector obstetrical providers and representatives of State government responsible for the delivery of health care to women and children. The major objectives of the AMCC is to improve access to obstetrical services for socially vulnerable women, both rural inhabitants and the medically indigent. The committee has been successful in serving as a forum in which to resolve many of the administrative problems that have arisen between private sector obstetrical providers and the State's Medicaid Program, the major source of payment for the one-third of pregnant women who are medically indigent. Building upon the trust that the committee members developed in working together, the AMCC served as a major force in persuading the State legislature to expand substantially its investment in perinatal care by increasing Medicaid eligibility, raising provider reimbursement, and improving social service for pregnant women. Such ad hoc coalitions between the private and public sector may be quite effective in addressing obstetrical access problems in other States.

Female↗

Addressing psychiatric comorbidity.

Research studies indicate that addressing psychiatric comorbidity can improve treatment for selected groups of substance-abusing patients. However, the chances for implementing the necessary techniques on a large scale are compromised by the absence of professional input and guidance within programs. This is especially true in public programs, which treat some of the most disadvantaged, disturbed, and socially destructive individuals in the entire mental health system. One starting point for upgrading the level of knowledge and training of staff members who work in this large treatment system could be to develop a better and more authoritative information dissemination network. Such a system exists in medicine; physicians are expected to read appropriate journals and to guide their treatment decisions using the data contained in the journals. Standards of practice and methods for modifying current practice are within the tradition of reading new facts, studying old ones, and comparing treatment outcome under different conditions with what is actually being done. No such general system of information-gathering or -sharing exists, particularly in public treatment programs. One of the most flagrant examples of this "educational shortfall" can be found among those methadone programs that adamantly insist on prescribing no more than 30 to 35 mg/day for all patients, in spite of the overwhelming evidence that these dose levels generally are inadequate. In some cases, program directors are unaware of studies that have shown the relationship between dose and outcome. In other cases, they are aware of the studies but do not modify their practices accordingly. This example of inadequate dosing is offered as an example of one situation that could be improved by adherence to a system of authoritative and systematic information dissemination. Many issues in substance abuse treatment do not lend themselves to information dissemination as readily as that of methadone dosing. However, the existence of a general information/education system about substance abuse treatment, combined with adherence to it among care providers, not only would provide helpful data for treatment staff but also might stimulate their curiosity and initiative. These later qualities, along with additions to existing treatment resources, may in the long run serve as the best guarantee for improvement. and maintenance of quality care.

Humans↗

The issues of transport multiplicity and energetics pertaining to methotrexate efflux in L1210 cells addressed by an analysis of cis and trans effects of inhibitors.

Studies are described addressing the controversial issue of the multiplicity of efflux routes for [3H]MTX in L1210 cells. We examined efflux multiplicity under conditions that do and do not maintain cellular ATP at the physiological level. In ATP-replete cells, the results delineate a probenecid-, bromosulfophthalein-, and verapamil-inhibitable route that accounts for nearly 90% of [3H]MTX efflux. Efflux of [3H]MTX by this route is inhibited by bromosulfophthalein in the trans orientation only, inhibited by probenecid only when present simultaneously in the cis and trans orientation and inhibited by verapamil only in the cis orientation. The remaining efflux of this folate analogue in ATP-replete cells appears to be mediated by the one-carbon, reduced folate system (MTX influx route), in that it is not inhibited by bromosulfophthalein or verapamil but is inhibited by the N-hydroxysuccinimide ester of MTX, a specific inhibitor of MTX influx, and a 10-fold higher concentration of probenecid than that required to inhibit ATP-dependent efflux. Under these conditions, MTX did not trans-stimulate [3H]MTX efflux. Also, no evidence was obtained for a putative bromosulfophthalein-insensitive, probenecid-inhibitable route for [3H]MTX efflux. In cells depleted to the extent of 90-95% of their ATP by 60-min incubation in medium in the absence of D-glucose and with 10 mM sodium azide, overall efflux of [3H]MTX was markedly reduced and appears to be mediated solely by the MTX influx route. Influx of [3H]MTX was both cis and trans inhibited by probenecid, and efflux under these conditions was markedly inhibited by the N-hydroxysuccinimide ester of MTX and trans-stimulated by MTX. Overall, the results of these studies are consistent with a model for methotrexate transport in L1210 cells derived [Dembo et al., J. Membrane Biol., 78: 9-17, 1984] in the authors' laboratory based solely upon a kinetic analysis of [3H]MTX influx and efflux in ATP-replete and depleted L1210 cells. As such, these new results identify a single ATP-dependent efflux route as the bromosulfophthalein-, probenecid-, and verapamil-inhibitable route in L1210 cells under conditions that maintain ATP levels at maximum.

Adenosine Triphosphate↗

Presidential address, 1990. Should general surgery be redefined?

The definition of general surgery, adopted by the Canadian Association of General Surgeons in 1983, has raised the expectations of the general surgical community. It was thought, at the time, that a definition that took into account the broad aspects of the specialty would make general surgeons more aware of their role in clinical and teaching activities, counteract the negative effects of subspecialization and prevent further fragmentation. Because of the many changes that have taken place in the 1980s, the author considered that a review of that definition was justified. To address this issue, the author has attempted to answer the following two questions: What are general surgeons doing in 1990? To what extent are they trained to do what they are supposed to do, according to the definition of general surgery? Data were obtained from la Régie de l'assurance-maladie du Québec in order to answer to the first question; with respect to the second, a questionnaire was sent to the chairmen of the 16 Canadian departments of surgery. The results of the study indicate that the definition of general surgery has not kept up with the times and should be revised. The author suggests that a modified definition should include primary and secondary components of the specialty in order to allow some flexibility. In the event that such a change seems appropriate, head and neck surgery should be only a secondary component of general surgery.

Canada↗

[Youths and the galaxy of questions raised by AIDS. Which themes to address?].

The spread of the AIDS pandemic urgently requires that we succeed in preventing HIV infection among the young. Much has been accomplished in information dissemination, sometimes leading to a sense of saturation. But the needs and request are still substantial when it comes to reflection, dialogue and action, both with and by the young, that is, through adult relays and peer leadership. The article presents a series of themes to be addressed with adolescents beyond the reductive equation "AIDS prevention = condom use." These are questions touching on the choice of lifestyles and relationships, and the concepts of risk, protection and responsibility.

Acquired Immunodeficiency Syndrome↗

[Complementary addressed alkylation of Escherichia coli 16S rRNA with 2',3'-O-[4-2-chloroethyl)-N-methylamino]benzylidene derivatives of deoxyribooligonucleotides. II. The nature of rapid interaction at 0 degrees C].

Fast non-covalent interactions of 16S rRNA Escherichia coli with 14C labeled 2',3'-O-[4-N-(2-chloroethyl)-N-methylamino]benzylidene derivatives of deoxyribooligonucleotides d(pACCTTGTT)rA, d[pTTACGATC)rU, d(pTTTGCTCCCC)rA (less than[14C]CHRCl-reagents) observed at 0 degrees C were investigated. It was shown, that 16S rRNA and [14C]CHRCl-reagents at 0 degrees C form stable complexes which can not be disrupted under mild acidic conditions (pH 4, 40 degrees C) and under denaturing conditions (7 M urea, 50 degrees C), but are completely disrupted in the course of centrifugation in sucrose density gradient in the presence of SDS. Formation of such complexes of 16S rRNA with greater than[14C]CHRCl-reagents at 0 degrees C was observed due to the presence in the reagent preparation of a number of unidentified products, formed in the course of the synthesis of benzylidene derivatives, and having a hydrophobicity larger, than those for greater than CHRCl-derivatives of deoxyribooligonucleotide. Preparation of [14C]CHRCl-reagents, subjected for purification by reverse-phase chromatography, were unable to form such a complex with 16S rRNA at 0 degrees C. Studies on the complementary addressed modification at 0 degrees C (or incubation at 0 degrees C) with the use of the oligonucleotide benzylidene derivatives not purified from hydrophobic contaminations may lead to alkylation within these complexes during subsequent treatments and in such a way give incorrect information about the level of alkylation within the complex under investigation.

Alkylation↗

[Activation by laser irradiation of a "switched on" oligonucleotide reagent for an addressed modification of nucleic acids].

Properties of oligonucleotide reagents containing an alkylating group of regulated reactivity (nitrogen mustard residue activatable upon mild borohydride reduction of the aromatic formyl group) have been studied. It was shown that these reagents can also be activated by irradiation with nitrogen laser light (lambda 337 nm). Activation of the reagent in complex with a target polydeoxyribonucleotide resulted in the addressed chemical modification of the target. The positional direction of the modification depended on the way of the activation (borohydride reduction or laser irradiation).

Alkylating Agents↗

Addressing the need for staff support among nurses caring for the AIDS population.

More and more nurses are caring for individuals with AIDS-spectrum disorders. When nurses become involved in hospital-based AIDS treatment, major psychosocial issues can arise. In settings where nursing personnel have limited or no experience working with patients with AIDS, fear of contagion is a major issue. This fear has both rational and irrational components. In general, providing up-to-date information in a small group setting can effectively reduce irrational fears. Rational fears, which are not as easily dealt with, should be a stimulus for behavior change (e.g., adoption of precautionary guidelines for reducing the possibility of accidental infection). Different issues arise among nurses specializing in AIDS care and include burnout, a sense of professional isolation, and the need to establish personal boundaries in dealing with patients. Guidelines are offered for establishing a group approach to address these concerns and to handle the sensitive issues that may arise.

Acquired Immunodeficiency Syndrome↗

Nursing home policies addressing the use or withdrawal of life-sustaining medical treatments.

There has been increasing interest in the use of nursing home policies and guidelines to improve decisions about the elective use of life-sustaining treatments. Such policies should be based on a sound and complete understanding of the legal and ethical governance responsibilities of health care facilities. Policies should address both the process of decision making and treatment plan implementation. Nursing home administrators should commission policies and monitor their implementation.

Aged↗

'Otology at the crossroads' (the second Morell MacKenzie address).

It is an honour for an otological surgeon to be asked to deliver the second Sir Morell MacKenzie address. Thank you for the invitation and for that honour. Exactly 100 years ago MacKenzie, with Norris Wolfenden, founded 'The Journal of Laryngology and Rhinology'. 'Otology' was not added to the title until 1892, the year MacKenzie died. I shall return to this theme later. It is also exactly 100 years since, in 1887, MacKenzie was asked by Queen Victoria to examine her son-in-law, Frederick, Crown Prince of Germany. The controversy and subsequent recrimination which flowed from the management of Frederick's laryngeal lesion I shall leave to future lecturers to assess. It is as the founder of British laryngology that he should be remembered. As early as 1863 he had started the Metropolitan Free Dispensary for Diseases of the Throat and Loss of Voice, the first institution of its kind in the world. He wrote authoritatively on diseases of the throat and invented many instruments for the difficult art of indirect laryngeal and pharyngeal surgery. He received his Knighthood, also in 1887.

History, 19th Century↗

[Complementary addressed modification of single- and double-stranded DNA by alkylating derivatives of oligonucleotides isolated by partial DNA fragmentation].

Reagents for complementary addressed modification of nucleic acids are proposed to be synthesized on the base of oligonucleotides obtained by partial chemical fragmentation of DNA. The alkylating 4-(N-2 chlorethyl-N-methylamino) benzyl-5'-phosphamide derivatives of 5'-[32P]-labelled oligonucleotides obtained from single and double-stranded DNA cloned in bacteriophage M13 mp9 have been synthesized. The alkylated derivatives of oligonucleotides selectively modify the complementary tracts of single-stranded DNA-target. They are also able to modify the complementary regions in double-stranded supercoiled plasmid DNA.

Alkylating Agents↗

[Complementary-addressed elimination of E1a sequence of simian adenovirus oncogene SA7 from circular single-stranded DNA of recombinant phage M13].

The G fragment of the simian adenovirus SA7 oncogene corresponding to E1a region was cloned into M13mp8 and M13mp9 phages. Single-stranded DNAs of the recombinant phages thus obtained (mp8G and mp9G) partially digested with DNAse II were used to synthesize polyalkylating derivatives capable of specific hybridisation and subsequent alkylation of complementary G sequences of corresponding phage DNAs. After incubation of complementary alkylated DNA in the presence of lysine, the preselected region (G fragment) was specifically eliminated without damaging vector sequences. The method of complementary-addressed cleavage proved to be useful for precise analysis of reactions of polyalkylating derivatives within complementary complexes.

Adenoviridae↗

Oliver Wendell Holmes: the professor and autocrat addresses medical matters.

Oliver Wendell Holmes, the physician, poet and novelist, was a frequent and at times outspoken commentator on the practice of medicine. His speeches and writings reveal Holmes's remarkable wit and facility in addressing such topics as medical education, drug prescription and medicine in society. Although delivered in the previous century his comments often seem to retain remarkable relevance in the current medical forum.

Curriculum↗

[Addressed modification of the promoter region of DNA in a complex with RNA polymerase by alkylating oligonucleotide derivatives].

Addressed chemical modification of double-stranded DNA unwound with the specific protein has been demonstrated. 4(N-2-chloroethyl-N-methylamino)benzyl-5'-phosphoamides of oligonucleotides d(CG)rC, d(ATCG)rC, d(AATCG)rC, which can serve as primers in the RNA polymerase-catalyzed transcription, alkylated A2 promoter region of pSK-A2 plasmid in its "open" complex with E. coli RNA polymerase.

Alkylating Agents↗

The 1979 Presidential Address. American Physical Therapy Association.

As I close this address, I do so with a certain sense of sadness about leaving a leadership team in a very exciting time of our professional history. I retire from this office with great faith in the leadership that will follow and with the optimism that the future will hold numerous excitements for our profession. The motivation and interactions that you have provided have caused me to dream of physical therapy in a manner I could have never envisioned on my own. Oh, how I thank you for the pleasures I have derived! I hope my remarks of today will serve to stimulate your dreams, your goals, inasmuch as the combination of our dreams and goals will bring greater fulfillment to the profession of physical therapy in the years that lie ahead.

Forecasting↗

[Synthesis and properties of membrane-addressed antioxidants based on phosphorylated pyrocatechols].

Amphiphilic membrane-addressed antioxidants differing in their hydrophobic-hydrophilic balance, 3,5-di-tert-butyl-2-hydroxyphenyl phosphate, (3,5-di-tert-butyl-2-hydroxyphenyl)hexadecyl phosphate, and (3,5-di-tert-butyl-2-hydroxyphenyl)-5-cholesten-3 beta-yl phosphate, were synthesized starting from 3,5-di-tert-butyl-o-quinone. Even at 10(-8) M concentration, 3,5-di-tert-butyl-2-hydroxyphenyl phosphate and (3,5-di-tert-butyl-2-hydroxyphenyl)hexadecyl phosphate inhibit formation of malonic aldehyde during peroxidation of lipids from rat brain homogenate initiated with a Fe(2+)-ascorbate system. At 10(-4) M and higher concentrations of antioxidants in the brain homogenate, the formation of malonic aldehyde is inhibited more efficiently than with tocopherol at the same concentrations.

Animals↗

Bioequivalence. An updated reappraisal addressed to applications of interchangeable multi-source pharmaceutical products.

This paper reviews study procedures for bioequivalence trials, mainly addressed to the New Drug Application (NDA) of generic drugs, strictly referring to EU and USA guidelines on this matter. Specific attention is devoted to the most appropriate experimental designs, the size of the volunteer sample, the ethical issues involved, statistics to assess bioequivalence and the accepted standard format for final research reports. Some aspects which create serious problems in bioequivalence trials, most of which not fully covered by the EU and USA specific guidelines, are comprehensively discussed. These include a) drugs with elevated variability; b) endogeneous substances and the management of baseline value; c) modified release formulations; d) prodrugs; e) restrictions to be contained in forthcoming guidelines on chiral medicinal products; f) superbioavailability; g) drugs with elevated half-life and h) cases in which bioequivalence trials should not be needed. As generic drugs cost less than the innovator product, agencies have facilitated their NDA procedures by requiring a dossier on chemistry and pharmacy and a pivotal bioequivalence study to demonstrate that the generic formulation is fully interchangeable with the innovator product. Bioequivalence is thus the key requirement for an NDA of a generic drug, and trials should be planned, conducted and reported in the most appropriate way. With this in mind, this review is an up-to-date reappraisal that should stimulate the attention of scientists and regulatory authorities on some open questions on bioequivalence.

Dosage Forms↗

Strengths-based case management. A role in addressing denial in substance abuse treatment.

A strengths-based approach to case management is being used as an intervention to assist persons with substance abuse problems to access needed resources. The same strengths-based practice activities that support resource acquisition are also effective in addressing the denial that can interfere with substance abuse treatment. Both benefits, resource acquisition and a constructive approach to denial, have shown promise for enhancing client participation in treatment and subsequent outcome from that treatment.

Denial, Psychological↗