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Biomedical subjects

R Baker

Publications and source records attributed to R Baker.

At least 307 records · Page 17Linked to original sources
PubMed1994

Quality assurance in general practice: the state of the art in Europe.

Quality assurance' (QA) is an important new development in general practice. In order to describe the state of the art in this field a preliminary survey was performed by the WONCA European Working Party on Quality in General Practice (EQuiP) in 17 European countries. The results revealed considerable differences in the systems and organization of general practice care [such as practice form, list size, the role of the general practitioner (GP), remuneration], which will have an impact on setting up QA. The preliminary findings demonstrated that most countries are only just beginning the implementation of QA. Nevertheless, there are many valuable developments and experiments concerned with the methodology, procedures and structures for it. In order to accelerate the speed of adoption of QA and to avoid the repetition of mistakes, policy makers and GPs from different parts of Europe should study examples in their fellow countries. A clearing house of QA projects in general practice can help to inform them on valuable developments.

Europe↗
PubMed1994

Cerebellar role in adaptation of the goldfish vestibuloocular reflex.

1. The time course of eye velocity responses elicited by head velocity steps was compared in normal, adapted, and cerebellectomized goldfish. Vestibuloocular reflex (VOR) adaptation was induced by combined visual and vestibular stimulation that altered the ratio of eye to head velocity (VOR gain) toward values either higher or lower than the control amplitude. The velocity step consisted of alternating periods of head rotation at a constant velocity of 16 degrees/s zero-to-peak around the vertical axis. 2. The VOR produced by head velocity steps consisted of an early acceleration-related component, the dynamic response, separated from a sustained period of constant velocity, the plateau, by a sag that occurred around 125-150 ms. Latency of the VOR averaged 18 ms for the adducting eye and 20 ms for abducting eye independent of the initial VOR gain. Adapted dynamic VOR responses diverged from the control records at the earliest detectable latency after both high and low VOR gain training. This result demonstrates modification in the shortest latency brain stem VOR pathway, presumably, the three-neuron reflex arc. 3. After acute cerebellectomy the adapted dynamic response was unaltered for approximately 50 ms in the low-gain and 70 ms in the high-gain VOR states. Not less than 30% of the altered velocity was retained throughout the remaining dynamic and sustained component. These results demonstrate that the vestibulocerebellum is not necessary for the maintenance of the earliest adapted eye velocity. Hence brain stem pathways are sufficient for the expression of the modified VOR. 4. Purkinje cells identified by simple and complex spikes were recorded extracellularly in the area of the vestibulocerebellum, where electrical stimulation produced conjugate ipsiversive horizontal eye movements. Independent eye and head velocity sensitivities were determined in response to visual world motion and VOR suppression, respectively. The two signals either added, canceled, or were both present in Purkinje cells throughout the range of eye velocity induced by vertical axis visual-vestibular stimulation. 5. Latency of Purkinje cell discharge to either a vestibular or visual velocity step exhibited means of 43 and 70 ms, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1994

Psychoanalysis as a lifeline: a clinical study of a transference perversion.

Case material from the analysis of a fetishistic cross-dresser is reported. The evolution of a transference perversion and treatment impasse, in the form of the recalcitrant symptom of anal flatulence, is described. The patient's contrasting needs to cling perversely and addictively to the analyst, on the one hand, and to provoke an acting out of the countertransference, on the other, are placed in the context of his dread of rejection and potentially suicidal reaction. The author argues in favour of offering psychoanalysis as a lifeline, but with the condition that the psychoanalytic setting and boundaries are maintained and that gratifications are denied. Limited but precise interpretive psychoanalytic work in the transference was maintained. The relatively good outcome is explained in terms of the provision of safety, survival of the analyst and avoidance of countertransference acting out, which, in the author's view, represents an implicit and mutative transference interpretation, the specific factor in bringing about psychic change. This enabled the patient to recognise and accept the analyst as a 'new' object and, as a consequence, to question and reject his idealisation of the anal universe that he inhabited.

Acting Out↗
PubMed1994

Vocal-acoustic pathways in a teleost fish.

Many teleost fish generate acoustic signals for vocal communication by the synchronized, high-frequency contraction of skeletal, sonic muscles. In midshipman, eight groups of brainstem neurons were distinguished after biocytin application to the sonic nerve that, we propose, represent the entire vocal motor circuit. Biocytin-filled terminals were ubiquitous within all areas containing labeled neurons and, together with ultrastructural evidence, suggested a serial, transneuronal transport at synaptic sites between at least three neuronal groups. The most intensely labeled neurons were positioned in the caudal brainstem and included a previously characterized pacemaker-motoneuron circuit and a newly recognized ventral medullary nucleus that itself gave rise to extensive commissural and lateral brainstem bundles linking the pacemaker circuitry to the rostral brainstem. Five additional groups formed a column rostrally within the medial brainstem adjacent to eighth nerve (octaval)-recipient nuclei largely presumed to be acoustic. This column extended dorsally up to the ventricular cell layer and as far anterior as midbrain isthmal levels. The best-defined group was in the octaval efferent nucleus that directly innervates the sacculus that is considered the auditory division of the inner ear. Saccular afferents and neurons throughout the medial column were also filled after biocytin application to the saccular nerve. This vocal-acoustic network overlaps low-threshold, electrical stimulation sites in the rostral brainstem that elicit vocalizations. The medial column must therefore be the origin of the descending pathway controlling activation of the vocal pacemaker circuitry and likely forms the basis for acoustically elicited vocalizations. We suggest this network, together with input from the pacemaker circuitry, is also the origin of a vocal-related, corollary discharge to acoustic nuclei. Direct links between vocal and acoustic brain regions are thus traits common to aquatic and terrestrial vertebrates.

Animals↗
PubMed1994

Abdominal colectomy offers safe management for massive lower GI bleed.

Preoperative localization of lower gastrointestinal (LGI) bleeding has been advocated on the presumption that lower morbidity and mortality are associated with limited colonic resection versus abdominal colectomy. However, extensive preoperative evaluation, especially when negative, may unnecessarily delay surgical therapy in the actively hemorrhaging patient. The purpose of this study was to analyze the mortality and morbidity associated with total abdominal colectomy (TAC) versus limited colonic resection (LIM), when performed for massive LGI hemorrhage. Sixty-one patients admitted for massive LGI bleeding (> or = 1 unit packed red blood cells (PRBCs) transfused preoperatively) over a 5-year period were analyzed. The following data was collected: preop PRBCs; total PRBCs; Apache score; age; resection type (LIM [n = 42] versus TAC [n = 19]); time elapsed before surgery; morbidity; and mortality. Patients in the TAC group received similar amounts of preoperative (4.1 +/- 0.8 units) and total (6.6 +/- 1.3 units) blood transfusions compared to the LIM group (3.3 +/- 0.4 units and 5.3 +/- 0.6 units). Overall, more time elapsed before surgery in the LIM group (95.4 +/- 13.0 hrs) compared with the TAC group (73.7 +/- 22.2 hrs) (P < 0.05 Student's t test). There was no significant difference in Apache score, age, or morbidity. Mortality rates were similar between the two groups (LIM 15%, TAC 6%). There was no instance of intractable diarrhea postoperatively in either group. The results indicate that TAC is a safe method of treating massive LGI hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1993

3-Acyl-4-hydroxyquinolin-2(1H)-ones. Systemically active anticonvulsants acting by antagonism at the glycine site of the N-methyl-D-aspartate receptor complex.

Most full antagonists at the glycine site of the NMDA receptor contain a carboxylic acid, which we believe to be detrimental to penetration of the blood-brain barrier. By consideration of a pharmacophore, novel antagonists at this site have been designed in which the anionic functionality is a vinylogous acid, in the form of a 4-hydroxyquinolin-2(1H)-one. In this series, a 3-substituent is necessary for binding, and correct manipulation of this group leads to compounds such as the 3-(3-hydroxyphenyl)propargyl ester 24 (L-701,273), with an IC50 for displacement of [3H]-L-689,560 binding of 0.17 microM and Kb against NMDA in the cortical slice of 1.39 microM. Compounds were tested for their ability to prevent audiogenic seizure in DBA/2 mice; the most potent compound in this series is the cyclopropyl ketone 42 (L-701,252), with an ED50 of 4.1 mg/kg ip. A model is proposed for binding to the glycine site, in which an important interaction is of a putative receptor cation with the pi-system of the 3-substituent.

Acylation↗
PubMed1993

3-Nitro-3,4-dihydro-2(1H)-quinolones. Excitatory amino acid antagonists acting at glycine-site NMDA and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.

3,4-Dihydro-2(1H)-quinolones, evolved from 2-carboxy-1,2,3,4,- tetrahydroquinolines and 3-carboxy-4-hydroxy-2(1H)-quinolones, have been synthesized and evaluated in vitro for antagonist activity at the glycine site on the NMDA receptor and for AMPA [(RS)-alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid] antagonist activity. Generally poor potency at the glycine site is observed when a variety of electron-withdrawing substituents are attached to the 3-position of 3,4-dihydro-2(1H)-quinolones. The analogues 5-9 (IC50 values > 100 microM, Table I) exist largely in the 3,4-dipseudoaxial conformation (as evidenced by 1H NMR spectra), whereas the 3-cyano derivative (10, IC50 = 12.0 microM) has a relatively high population of the 3-pseudoequatorial conformer. The 3-nitro analogue (4, IC50 = 1.32 microM) has a pKa approximately 5 and thus exists at physiological pH as an anion with the nitro group planar to the quinolone ring. The general requirement of acidity for high affinity binding at the glycine/NMDA site is supported with the good activity of the other 3-nitro derivatives (13-21), all of which are deprotonated at physiological pH. The 3-nitro-3,4-dihydro-2(1H)-quinolones and 2-carboxy-1,2,3,4-tetrahydroquinolines show quite different structure-activity relationships at the 4-position. The unselective excitatory amino acid activity of 21 is comparable with 6,7-dichloro-quinoxaline-2,3-dione and 6,7-dichloroquinoxalic acid and this suggests similarities in their modes of binding to excitatory amino acid receptors. The broad spectrum excitatory amino acid antagonist activity of the 4-unsubstituted analogue 21 (KbNMDA = 6.7 microM, KbAMPA = 9.2 microM) and the glycine/NMDA selectivity of the other 3-nitro derivatives allows the proposal of a model for AMPA receptor binding which differs from the glycine binding pharmacophore in that there is bulk intolerance adjacent to the 4-position. Compound 21 (L-698,544) is active (ED50 = 13.2 mg/kg) in the DBA/2 mouse anticonvulsant model and is the most potent combined glycine/NMDA-AMPA antagonist yet reported, in vivo, and may prove to be a useful pharmacological tool.

Amino Acids↗
PubMed1993

Synthesis and serotonergic activity of 5-(oxadiazolyl)tryptamines: potent agonists for 5-HT1D receptors.

The synthesis and 5-HT1D receptor activity of a novel series of 5-(oxadiazolyl)tryptamines is described. Modifications of the oxadiazole 3-substituent, length of the linking chain (n), and the amine substituents are explored and reveal a large binding pocket in the 5-HT1D receptor domain. Oxadiazole substituents such as benzyl are accommodated without loss of agonist potency or efficacy. The incorporation of polar functionality on a phenyl or benzyl spacer group results in a 10-fold increase in affinity and functional potency. Optimal 5-HT1D activity is observed when the heterocycle is conjugated with the indole and the benzyl sulfonamides 20t and 20u represent some of the most potent 5-HT1D agonists known. Replacement of O for S in the heterocycle leads to a further increase in potency. Deletion of oxadiazole N-2 does not reduce activity, suggesting the requirement for only one H-bond acceptor in this location. The selectivity of these compounds for 5-HT1D receptors over other serotonergic receptors is discussed. Sulfonamide 20t shows > or = 1000-fold selectivity for 5-HT1D over 5-HT2, 5-HT1C, and 5-HT3 receptors and 10-fold selectivity with respect to 5-HT1A receptors. The functional activity of this series of compounds is studied and demonstrates high 5-HT1D receptor potency and efficacy comparable to that of 5-HT.

Animals↗
PubMed1993

Cyclic peptides as selective tachykinin antagonists.

Twenty homodetic cyclic peptides based on the C-terminal sequence of substance P were prepared (Table I) by a combination of solid-phase techniques and cyclizations using azide coupling procedures. Incorporation of dipeptide mimics based on substituted gamma-lactams were used in some cases to restrict their conformational mobility. Five of these cyclic peptides were shown to have high tachykinin antagonist activity (pA2 > 6) at NK-2 receptors (rat vas deferens). The two most potent of this series, XVII, cyclo(Gln-Trp-Phe-Gly-Leu-Met) (pA2 = 8.1), and I cyclo(Gln-Trp-Phe(R)Gly[ANC-2]Leu-Met) (pA2 = 6.7), were selective for NK-2 receptors compared with the other tachykinin receptors (Table II).

Amino Acid Sequence↗
PubMed1993

Visibility and the just allocation of health care: a study of age-rationing in the British National Health Service.

The British National Health Service (BNHS) was founded, to quote Minister of Health Aneurin Bevan, to 'universalize the best'. Over time, however, financial constraints forced the BNHS to turn to incrementalist budgeting, to rationalize care and to ask its practitioners to act as gatekeepers. Seeking a way to ration scarce tertiary care resources, BNHS gatekeepers began to use chronological age as a rationing criterion. Age-rationing became the 'done thing' without explicit policy directives and in a manner largely invisible to patients, to Parliament, and to the public. The invisibility of the practice, however, violates the publicity principle that John Rawls and other philosophers believe essential to fairness. BNHS invisible age-rationing practices are thus a test case of the principle that fairness presupposes publicity; they raise the question: is it possible to preserve equitability in a system that uses non-public criteria to allocate scarce resources? To seek an answer, published data on access to end-stage renal disease (ESRD) treatment in Britain and the European Community (EC) are analysed. Among the findings are: that BNHS age-rationing acts as an excuse for denying care to those most likely to need ESRD treatment; and is, moreover, arbitrary and inequitable. It is further argued that no age-rationing policy can sustain visibility, and that, if the BNHS is to be fair to its patients, it must reform its present age-rationing practices, replacing them by a publicly visible, outcome-based rationing policy that rations either in terms of QALYs or triage categories.

Age Factors↗
PubMed1993

The design of novel muscarinic partial agonists that have functional selectivity in pharmacological preparations in vitro and reduced side-effect profile in vivo.

Antagonist/agonist binding ratios (NMS/Oxo-M ratio) were used as an index of the efficacy of novel compounds acting at muscarinic receptors. These binding ratios have been used with a range of functional pharmacological assays to investigate the effects of varying the efficacy of muscarinic agonists. This strategy has been used as a means of obtaining functional receptor selectivity by exploiting differences in effective receptor reserves. The oxadiazole and pyrazine muscarinic agonists L-670,548 (NMS/Oxo-M ratio 1100) and L-680,648 (NMS/Oxo-M ratio 690) are amongst some of the most potent and efficacious agonists known. Decreasing the efficacy of compounds from these series, resulted in compounds with functional selectivity. The chloropyrazine L-689,660 (NMS/Oxo-M ratio 28) was an agonist on the rat superior cervical ganglion (M1), a partial agonist on the guinea-pig ileum (M3), but was an antagonist in the guinea-pig atria (M2). Synthesis of compounds with even lower predicted efficacy, such as the cyclopropyloxadiazole L-687,306 (NMS/Oxo-M ratio 15), maintained agonist activity in the ganglion, but showed antagonist activity in the M3 ileal, as well as the M2 atrial preparations. When tested in vivo these compounds did not produce many of the side effects associated with more efficacious agonists, particularly those associated with the cardiovascular system. However, they were active in reversing scopolamine-induced deficits in a variety of behavioural paradigms. This approach shows how functional selectivity for muscarinic receptor subtypes can be achieved in vitro, that in vivo reduces the dose-limiting side effects normally associated with muscarinic agonists.

Animals↗
PubMed1993

MAAGs (Medical Audit Advisory Groups): the Eli Lilly National Clinical Audit Centre.

Outlines the framework for promoting audit in general practice, created as one part of the health service reforms. Medical Audit Advisory Groups (MAAGs) were set up in each district with the aim of participation in audit of all general practitioners by April 1992. The activities undertaken have included those recommended by the Department of Health; the most significant of these being the appointment of lay facilitators who are able to assist general practitioners and primary care teams co-operate over efforts to improve the quality of care, and may offer one means of introducing some of the methods of total quality management into general practice. Discusses the problems which remain: audit is not yet sufficiently systematic, interface audit with secondary care is at a very early stage, the ways to involve managers and patients in audit remain to be clarified, and there is little evidence of the consequences of audit in terms of improved care. The Eli Lilly National Clinical Audit Centre has been set up within the Department of General Practice, University of Leicester, in order to address these issues.

Family Practice↗
PubMed1993

Conservation of neuroepithelial and mesodermal segments in the embryonic vertebrate head.

The organization of embryonic efferent cranial nerves is addressed here by interspecies comparison of segmentally patterned neuromeres, efferent neuronal populations and early mesodermal sources of target muscles. The segmental constancy of these three structural patterns is evaluated for elasmobranch, teleost, reptile, bird and mammal embryos and compared with the segmentally restricted expression patterns of Hox genes. A conserved series of hindbrain neuroepithelial segments (rhombomeres) is present in all of these taxa. Dye-labeling experiments demonstrate that the segmental locations of efferent neurons projecting through individual cranial nerves are likewise highly conserved. Notable segmental variation is however shown in the location of the VI and IX-XII motoneurons, suggesting the likelihood of homeotic-like changes in relations between rhombomere and neuronal 'identity' during vertebrate evolution. Since experimentally induced shifts in expression borders of Hox genes appear to be correlated with alterations in segment identity and/or neuronal phenotype, the need for further examination of segmental locations of specific neuronal groups and the segmental expression patterns of Hox genes between species is emphasized. Comparison of early cranial mesodermal subdivisions in elasmobranchs with descriptions of somitomeres in amniotes suggests that a series of axially unique mesodermal populations may also be conserved throughout vertebrates. The possibility is raised that common mechanisms of axial specification may underlie the initial appearance of segmental patterning in both neural and mesodermal layers during gastrulation. Implications of these conserved patterns for understanding the phylogenetic origin of the vertebrate head are briefly discussed.

Animals↗
PubMed1993

Analysis of T helper and antigen-presenting cell functions in cord blood and peripheral blood leukocytes from healthy children of different ages.

The development of antigen-specific functional T lymphocyte immunity in infants and children is an area of immunology that needs elucidation. Leukocytes from cord blood (CBL) and from PBL of children of different ages who were in the hospital for minor surgical procedures were compared with PBL from healthy adults for their ability to generate T helper cell (Th) responses assessed by in vitro proliferation and IL-2 production after stimulation with: influenza A virus (FLU); tetanus toxoid (TET); adult allogeneic PBL that were either undepleted (ALLO) or depleted of adherent antigen presenting cells (ALLONW); and PHA. CBL generated Th responses to ALLONW, ALLO, and PHA, but not to FLU or TET. PBL from infants between 6 and 13 mo of age responded to ALLO and PHA; none responded to FLU or ALLONW, and two of four responded weakly to TET. PBL from children between 13 and 26 mo of age responded to all stimuli except FLU, to which only one child responded marginally. PBL from children older than 36 mo responded to all stimuli at levels comparable to those of PBL from adults. The use of undepleted and adherent cell-depleted CBL and PBL from children of different ages as allogeneic stimulators of responses generated by PBL from adults indicated that the antigen presenting function of CBL and PBL from children 13 mo or older are sufficiently developed to present alloantigen, whereas PBL from children younger than 13 mo are not. Therefore, our results indicate that age-dependent differences exist in both T helper and antigen-presenting functions of CBL and PBL from children of different ages. Surprisingly, CBL appear to be more efficient in antigen-presenting function than PBL from children younger than 13 mo. These findings are important for establishing developmental parameters of T helper cell immunity relevant for pediatric infection and transplantation in infants and children.

Adult↗
PubMed1993

Ethical issues faced by clinician/managers in resource-allocation decisions.

This article explores the ethical issues faced by clinicians with management responsibilities (clinician/managers) when making decisions related to resource allocation and utilization at a Canadian teaching hospital. Using a focus group method, 28 individuals participated in four homogeneous groups that included nurse managers, managers from other professional groups, and physician managers. Ethical issues that recurred throughout the discussions included fairness, concern with preventing harm, consumer/patient choice, balancing needs of different groups of patients, conflict between financial incentives and patient needs, and professional autonomy. The particular issue of conflict is analyzed from two perspectives--a theory of professional-bureaucratic roles and of obligation--that illustrate how both management and philosophical issues are related. The findings suggest that decentralizing resource allocation and utilization decisions does raise ethical issues for clinician/managers and that a better understanding of these issues can be obtained using an interdisciplinary perspective.

Canada↗