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Biomedical subjects

J Buchanan

Publications and source records attributed to J Buchanan.

At least 19 recordsLinked to original sources

Morphologically docked synaptic vesicles are reduced in synaptotagmin mutants of Drosophila.

Nerve terminal specializations include mechanisms for maintaining a subpopulation of vesicles in a docked, fusion-ready state. We have investigated the relationship between synaptotagmin and the number of morphologically docked vesicles by an electron microscopic analysis of Drosophila synaptotagmin (syt) mutants. The overall number of synaptic vesicles in a terminal was reduced, although each active zone continued to have a cluster of vesicles in its vicinity. In addition, there was an increase in the number of large vesicles near synapses. Examining the clusters, we found that the pool of synaptic vesicles immediately adjacent to the presynaptic membrane, the pool that includes the docked population, was reduced to 24 +/- 5% (means +/- SEM) of control in the sytnull mutation. To separate contributions of overall vesicle depletion and increased spontaneous release from direct effects of synaptotagmin on morphological docking, we examined syt mutants in an altered genetic background. Recombining syt alleles onto a second chromosome bearing an as yet uncharacterized mutation resulted in the expected decrease in evoked release but suppressed the increase in spontaneous release frequency. Motor nerve terminals in this genotype contained more synaptic vesicles than control, yet the number of vesicles immediately adjacent to the presynaptic membrane near active zones was still reduced (33 +/- 4% of control). Our findings demonstrate that there is a decrease in the number of morphologically docked vesicles seen in syt mutants. The decreases in docking and evoked release are independent of the increase in spontaneous release. These results support the hypothesis that synaptotagmin stabilizes the docked state.

Animals

Outcome study of prehospital patients signed out against medical advice by field paramedics.

STUDY OBJECTIVE: To describe the incidence and demographic data of prehospital patients who contact paramedics by way of the 911 system, refuse transport against medical advice (AMA), then call 911 and are subsequently reevaluated by paramedics in the following 48 hours. METHODS: We conducted a retrospective observational review of records using the San Diego County Quality Assurance Network database for prehospital providers. All paramedic 911 responses that made base hospital contact over a 3-month period were reviewed to identify patients who signed out AMA. The main outcome measure was to identify patients who signed out AMA and then called 911 again within 48 hours. The demographics, complaints, treatments, and dispositions of these patients are described. RESULTS: Of 6,512 total 911 responses reviewed, 443 (7%) involved patients who signed out AMA. Of these patients, 156 cases (35.2%) were listed as trauma and 287 (64.8%) were medical, with cardiac chest pain, seizure, and respiratory distress/shortness of breath the most frequently noted medical subcategories. Fifty-one (11.5%) such patients received treatment; 34 received dextrose, 12 naloxone, 4 albuterol, and 1 a splint. Patient names were available in 5,515, of the total 6,512 responses and 431 of the 443 AMA cases, permitting computer searching of reevaluations by paramedics. Of the 431 AMA patients for whom a name was available, 10 (2%) called 911 again within 48 hours. All 10 callbacks were made for a related chief compliant, and all 10 of these patients were transported (4 admitted to hospital, 1 died en route, 1 transferred to another facility, 4 discharged from the ED). Of these 10 patients, 7 (70%) were older than 65 years, compared with 17% of all AMA patients older than 65 years. CONCLUSION: On the basis of our findings, patients over the age of 65 years have a propensity to recontact paramedics and should be aggressively encouraged to seek emergency medical treatment. Future prospective studies should be mounted to examine at patient outcome and to assess why patients sign out AMA after making contact with paramedics.

Adolescent

RT-PCR based diagnosis and molecular characterisation of mumps viruses derived from clinical specimens collected during the 1996 mumps outbreak in Portugal.

Clinical specimens collected during an outbreak of mumps were characterised by RT-PCR, nested PCR, and nucleotide sequencing. Mumps virus was positively identified in 12/21(57%) saliva, 9/21(43%), throat and 1/33(3%) urine specimens and further sequence comparison revealed that at least six strains of viruses, which differed from 0-9.43% at the nucleotide levels, were cocirculating during the epidemic. However, phylogenetic analysis showed that these viruses grouped with two previously identified lineages which were mostly composed of other European mumps virus isolates.

Adolescent

Clustering of mumps virus isolates by SH gene sequence only partially reflects geographical origin.

The nucleotide sequences of the SH gene of 45 new mumps virus isolates derived from different parts of Europe, Canada and USA were determined. A phylogenetic tree was constructed which confirmed the existence of three major clusters. While clustering according to geographical origin was clear in some cases each of the major clusters included isolates which were widely separated in origin. The degree of variability between the sequences of SH genes of different strains and the ratio of coding to non coding differences were both very high compared to those observed in other genes such as the M and HN. A standardized system of nomenclature of mumps strains was established.

Amino Acid Sequence

Voices from practice: mental health nurses identify research priorities.

Through a collaborative research project, nurse clinicians and nurse academics identified and prioritized the most important research questions arising from the current and future practice of mental health nurses in an eastern Canadian region. Study methods included the Delphi technique and a nominal group survey approach. Nine categories of research questions emerged. The top four categories are discussed under the headings: Preparation of Helpers, the Service System, Caregiver Needs, and Clients With Major Behavior Problems. This timely study offers explicit direction for psychiatric and mental health nursing practice and research, and for the development of social policy.

Attitude of Health Personnel

Patients' beliefs about cancer management.

The results of a questionnaire answered by 205 medical patients are reported (100 patients with cancer and 105 with other medical conditions). The questionnaire examined beliefs and preferences regarding various aspects of cancer, including expectations of medical management and treatment. The issues examined relate to beliefs and preferences about information giving, trust of doctors' control of decision making, expectations of help, expectations of treatment, the treatment of cancer pain including morphine use, and issues of terminal care. Some patients appear to hold the inconsistent beliefs that doctors should tell them all they want to know, but that doctors do not know a lot of what they would like to be told. They were also ambivalent about who should make decisions, patient or doctor, suggesting a preference for collaborative consensus decision making. It may be important to inform patients more clearly about what doctors can and cannot reasonably be expected to know and do. Some incorrect beliefs about management were related to fear about having cancer. The results suggest the need for better communication between patients and their professional carers and the need for accessible health information about cancer management to be available to the general public.

Adult

Comparison of access and costs of Medicaid dental services in a hospital clinic and community practices.

OBJECTIVES: This paper reports the results of a three-year evaluation of access to dental care and its associated costs for Aid to Families with Dependent Children (AFDC) beneficiaries enrolled in a hospital-based health maintenance organization (HMO) or a fee-for-service (FFS) option. METHODS: Medicaid enrollees (n = 3, l655) having a year of eligibility were assigned to either the hospital HMO or FFS care, and their use of dental care and its costs compared. RESULTS: A higher percent of those beneficiaries enrolled in the FFS option used dental care than those in the HMO plan. FFS enrollees also had more annual visits per person than those in the randomly assigned HMO group. FFS dental patients treated in the hospital had the highest costs of any payment-provider combination studied. CONCLUSIONS: To understand the mix of utilization rates, visits, and costs, one must take into account the way in which the HMO hospital plan is reimbursed, the way in which the dental department is reimbursed, and the way in which the dental provider is reimbursed.

Adolescent

Social support and schizophrenia: a review of the literature.

Within an interactive model of schizophrenia, social support is postulated to serve as a protective factor that facilitates coping and competence, thus modulating the deleterious effects of social and environmental stressors. Although there is growing evidence of the importance of social support in influencing the course of schizophrenia, the evidence suffers from many methodological weaknesses including vagueness in the conceptualization, operations, and measurement of the construct. These are discussed from the perspective of the social support research in general, and from the social support-schizophrenia perspective. Despite the wide range of research approaches and methodological problems encountered, common threads in respect to social support are found.

Humans

Increased instability of intermediate alleles in families with sporadic Huntington disease compared to similar sized intermediate alleles in the general population.

We have directly compared intergenerational stability of intermediate alleles (IAs) derived from new mutation families (IANM) for Huntington disease (HD) with IAs in the general population (IAGP) which occur in approximately 1 in 50 persons. Analysis of meiotic events in blood and sperm reveals that IANM are significantly more unstable than IAGP despite similar size. However, for both IANM and IAGP CAG changes were small and risks for inheriting an expansion into the HD affected range were low. Sequence analysis reveals that the CAG tract is generally interrupted by a penultimate CAA in IAGP, IANM and alleles in the affected range. In one new mutation family, however, two A-->G mutations result in a pure CAG tract which is associated with very marked instability. These mutations alter the predicted DNA hairpin structure with a predicted increase in the likelihood of large expansion, supporting the model that hairpin loop formation plays an important role in trinucleotide instability.

Alleles

Technical feasibility of genetic testing for Alzheimer's disease.

This article examines the feasibility of using molecular genetic information for diagnostic and predictive testing in Alzheimer's disease (AD). The scope is limited largely to early onset familial cases, but a brief update on genetic research in late onset disease is included. The usefulness and accuracy of such testing is determined by the results and interpretation of current research data which are presented herein. The ethical and legal issues implicated in such procedures are not covered but are examined elsewhere in this issue. During the course of the genetic analysis of AD, it has become clear that it is an etiologically heterogeneous disorder. In understanding the genetic predisposition to AD there should be continual attention to this message. Age of onset and familiality have emerged as the most useful clinical features demarcating subgroups with common origins. At least two genes predispose (independently) to early onset familial AD: the beta-amyloid precursor protein gene (beta APP) and an unidentified gene on chromosome 14. Germ line mutations in these genes act dominantly. The accurate use of genetic data in AD, for diagnostic, screening and predictive purposes relies on the most up-to-date knowledge of the transmission of the disorder in relation to mutations in these genes. The interpretation of genetic data is examined for each of the known early onset genes. In addition, we review the data pertaining to late onset disease and risk conferred by the APOE locus to both familial and nonfamilial cases. The use of these data in genetic risk analysis must be reserved until a full explanation of the association and its meaning is forthcoming. Isolated cases of AD occur at all ages of onset, but no AD mutations in the beta APP gene have yet been identified in isolated cases.

Adult

Distinguishing between multiple personality disorder (dissociative identity disorder) and schizophrenia using the Structured Clinical Interview for DSM-IV Dissociative Disorders.

The authors describe the systematic assessment of dissociative symptoms using the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) in 50 psychiatric outpatients with a referring DSM-III-R diagnosis of either schizophrenia or schizoaffective disorder (N = 31) and subjects with multiple personality disorder (MPD [DSM-IV name change: dissociative identity disorder]; N = 19). Results indicate that patients with MPD experience significantly higher scores for five specific dissociative symptoms than patients with schizophrenia or schizoaffective disorder. The range, severity, and nature of the five dissociative symptom areas evaluated by the SCID-D distinguish MPD from the occasional occurrence of dissociative symptoms which may be seen in schizophrenia. Systematic assessment of dissociative symptoms using the SCID-D can assist in accurate differential diagnosis of MPD and schizophrenia.

Adult

Mossy fiber growth and synaptogenesis in rat hippocampal slices in vitro.

Hippocampal slices from early postnatal rat were used to study mossy fiber (MF) growth and synaptogenesis. The ability of MFs to form new giant synapses within isolated tissue slices was established by a series of experiments involving synapsin I immunohistochemistry, electron microscopy, and whole-cell recordings. When hippocampal slices from immature rats were cultured for up to 2 weeks, the distribution of giant MF terminals was similar to that found in vivo. Using a lesioning procedure, we determined that MFs in slices extend and form appropriate synaptic connections with normal target CA3 pyramidal cells. MF terminals were dispersed more widely than normal within the CA3 pyramidal layer after a lesion, but electron microscopy indicated that synaptic junctions were still primarily associated with pyramidal cell dendrites and not the somata. Establishment of functional synaptic input in vitro was confirmed by whole-cell recordings of MF-driven excitatory postsynaptic currents (50 pA to 1 nA) in pyramidal cells. The results establish for the first time that an MF projection with appropriate and functional synaptic connections can be formed de novo and not just maintained in excised hippocampal slices. The cellular dynamics underlying MF growth and synaptogenesis were examined directly by time-lapse confocal imaging of fibers selectively stained with a fluorescent membrane dye (Dil or DiO). MFs growing deep within isolated tissue slices were tipped by small (5-10 microns), active growth cones that advanced at variable rates (5-25 microns/hr). Furthermore, dynamic filopodial structures were seen at small varicosities along the length of developing MFs, which may identify nascent en passant synaptic contacts. The hippocampal slice preparations are shown to support normal development of MF connections and allow for direct visualization of the cellular dynamics of synapse formation in a mammalian CNS tissue environment.

Animals

Mutations of the p53 gene do not occur in testis cancer.

To characterize the role of p53 in the development of testis cancer, we looked for mutations in the coding sequences of the p53 gene. DNA was obtained both from familial and sporadic testis cancer specimens, as well as from peripheral blood from members of a testis cancer kindred. Mutations in the p53 gene were screened using a combination of constant denaturant gel electrophoresis and single-strand conformational polymorphism analysis, 2 screening methods that can detect single base changes. Abnormalities detected by these methods were confirmed by sequencing of the corresponding cloned polymerase chain reaction products. All conserved regions of the p53 coding sequences were examined, encompassing all previously reported sites of mutations. No mutations were found in any of 22 germ cell cancers of the testis or in the germline DNA of 17 members of the testis cancer family. This is in striking contrast to most other human cancers, in which mutations of p53 are the most commonly described molecular event associated with tumorigenesis. We conclude that dysfunction of tumor suppressor gene or genes other than p53 may prove to play an important role in the development of germ cell cancers of the testis.

Genes, p53

Designer hips.

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Adult

The spatial distribution of calcium signals in squid presynaptic terminals.

1. The fluorescent Ca2+ indicator dye, fura-2, was used to examine the spatial distribution of intracellular Ca2+ signals in giant presynaptic terminals of squid. Brief trains of presynaptic action potentials were evoked to open Ca2+ channels within the giant presynaptic terminals and elevate presynaptic Ca2+ concentration. 2. Electrical stimulation produced pronounced rises in presynaptic Ca2+ concentration. These rises were much larger in the terminal region than in the adjacent axonal region of the presynaptic neuron, suggesting that Ca2+ channels are most abundant in the terminal. 3. Stimulation also produced gradients in Ca2+ concentration across the width of the presynaptic terminal. During stimulation, Ca2+ concentration was highest in the compartment of the presynaptic terminal closest to the postsynaptic neuron. This suggests that the Ca2+ channels are localized to this region of the presynaptic terminal. 4. Following the end of action potential trains, the rises in Ca2+ concentration became uniform across the width of the terminal. The redistribution of Ca2+ presumably is due to diffusion of Ca2+ throughout the presynaptic cytoplasm. Stimulus-evoked rises in Ca2+ declined slowly over several tens of seconds. 5. Histological examination of a giant presynaptic terminal used for imaging experiments revealed that the spatial compartments where stimulus-induced rises in Ca2+ concentration were highest were also enriched in active zones, the presynaptic sites of transmitter secretion. The co-localization of Ca2+ transients and active zones strongly suggests that neurons cluster Ca2+ channels selectively at active zones and that they do so to enhance the magnitude of Ca2+ signals in the vicinity of the active zone. 6. Longitudinal gradients in Ca2+ concentration also occur within presynaptic terminals and can be quantitatively accounted for by gradients in surface/volume ratio and density of active zones along the length of the presynaptic terminal.

Action Potentials

Multiple personality disorder in criminal law.

The authors review the recent literature on multiple personality disorder (MPD), the most severe and chronic of the dissociative disorders, in relation to court cases of competence to stand trial, the insanity defense, and research on malingerers feigning MPD. Issues relevant in the assessment of competency and insanity are described. Features characteristic of MPD, including amnesia and alterations in consciousness and personality, have varying degrees of influence over the criminal behavior of an individual with MPD. As in other psychiatric disorders, the influence of MPD on an individual's competence to stand trial, and sanity, can be evaluated systematically. This article discusses a specific diagnostic tool, the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D), an extensively field tested instrument that is potentially quite useful in forensic assessment of suspects manifesting dissociative symptoms and disorders. The particular advantages of the SCID-D will be reviewed in the context of some well known criminal cases involving MPD. Further research using diagnostic interviews for the systematic assessment of dissociative symptoms and MPD in criminal cases will continue to clarify the influence of these symptoms in a forensic context.

Adult

The teacher-student relationship: the heart of nursing education.

This author has witnessed many nurses entering the university unhappy, feeling an outside pressure (e.g., the nursing profession) rather than a personal need, to do so. Nurses return to school often at great personal expense, adding one more role to an already full family and work life. Most nurses study part-time, and do not necessarily have the support of their peers in the workplace as they embark on this journey. A tradition of expecting authority, and a technical training background are added to the factors that create a profile which is not atypical of a returning-to-school nurse. Assisting these nurses to continue to grow and to flourish as nurses, as learners, and as persons involves a reframing of the process and the products of learning. Teaching must become a process of evoking possibilities and meaning for the individual student, while validating and using the richness of the experience that the student brings to the setting.

Education, Nursing, Baccalaureate