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Biomedical subjects

P Barr

Publications and source records attributed to P Barr.

At least 19 recordsLinked to original sources

An evaluation of the autopsy following death in a level IV neonatal intensive care unit.

OBJECTIVE: To ascertain the determinants of neonatal autopsy, define clinical errors in the causes of death, and elucidate the possible audit and genetic value of the autopsy following death in a Level IV neonatal intensive care unit (NICU). METHODS: A review and correlation of clinical and autopsy information in a case series of infants who died during the period 1991-97. RESULTS: Two hundred and twenty-nine of 4057 infants admitted to the NICU died and 91 (39.7%) underwent an autopsy. The underlying cause of death was significantly different in infants who had an autopsy compared with infants who did not (P = 0.02). The autopsy rate was higher for deaths from miscellaneous causes (52.9%), lethal malformation (46.8%) and infection (45.4%) than deaths from prematurity (25.9%) and asphyxia (19%). Clinical errors in the causes of death were found in 22% of the infants, and in 4.4% a change in management may have been curative or prolonged life. The autopsy had audit value in 26% of infants and genetic value for a single gene (Mendelian) disorder in 4.4%. CONCLUSIONS: Although the autopsy following death in a Level IV NICU yields potentially useful information in more than one-third of cases, this does not seem sufficient to ensure a high neonatal autopsy rate.

Australia

The use of lumbar puncture and laboratory tests for sepsis by Australian neonatologists.

OBJECTIVE: To ascertain the current use of lumbar puncture (LP) and laboratory tests for possible or suspected sepsis by Australian neonatologists. METHODS: A self administered anonymous response questionnaire. RESULTS: Sixty-nine (73%) of 94 neonatologists responded. None performed LP routinely in preterm infants with respiratory distress syndrome (RDS) or asymptomatic term infants with maternal Group B streptococcus (GBS) colonisation. One (1.6%) performed LP in term infants with respiratory distress, and only 35 (51%) performed LP in preterm infants with suspected late-onset sepsis (LOS). Twenty-one percent did not perform LP on all preterm infants with RDS and septicaemia and 24% did not perform LP on all preterm infants with late-onset septicaemia. Sixty-six percent and 85% did not perform LP for laboratory evidence suggestive of sepsis in preterm infants with RDS and preterm infants with LOS, respectively. Forty-nine percent investigated asymptomatic term infants with maternal GBS colonisation. CONCLUSIONS: Lumbar puncture and laboratory tests for possible or suspected sepsis are not used uniformly by Australian neonatologists. The presently available information in the scientific literature is ambiguous and systematic review and further scientific study are required to determine best practice guidelines.

Australia

Cardiopulmonary resuscitation in the newborn intensive care unit.

OBJECTIVES: To determine the outcome for cardiopulmonary resuscitation (CPR) following cardiac arrest, and the predictors of response to CPR, in newborn infants with a diverse range of medical, surgical and cardiological problems cared for in a tertiary level newborn intensive care unit (NICU). METHODOLOGY: Infants who had suffered a cardiac arrest and received CPR were identified by retrospective review of the NICU medical records. RESULTS: Thirty-five (1%) of 3624 infants admitted to the NICU during a six-year period received CPR because of a cardiac arrest. Twenty (57%) of the infants did not respond to CPR and died within 2.5 h (non-responders), eight (23%) responded to CPR but died before discharge from hospital (short-term responders), and seven (20%) responded to CPR and were discharged from hospital (long-term responders). The arterial pH was significantly lower in non-responders to CPR compared with responders. Non-responders to CPR were not significantly different from responders with regard to gestational age, birth weight, age at arrest, systolic blood pressure, blood gases, severity of respiratory failure, or renal function. In 24 infants (68%), the precipitating cause for the cardiac arrest was either irreversible (20), or not known (4) and all died prior to discharge from hospital. In 11 infants (32%), the cardiac arrest was considered to have been precipitated by an acute and reversible event, and seven (64%) survived to discharge from hospital. All six infants with septicaemic shock were non-responders to CPR. Three of 15 infants with complex congenital heart disease were long-term responders to CPR but none survived without a major physical and psychomotor disability. CONCLUSION: The present study offers support for the recommendation that CPR may be withheld in infants who do not have a reversible cause for their cardiac arrest but are dying or will die soon from the inexorable progress of their illness.

Cardiopulmonary Resuscitation

Fine epitope specificity of antibodies to region II of the Plasmodium vivax circumsporozoite protein correlates with ability to bind recombinant protein and sporozoites.

Recent work has suggested that important B- and T-cell epitopes on the circumsporozoite protein (CSP) of Plasmodium vivax lie external to the major repeat regions of the protein. We have studied two naturally exposed human populations (Caucasian and Papua New Guineans) and determined the antibody response to yeast-derived recombinant CSPs, overlapping synthetic peptides spanning amino acids 76 348 of the Belem P. vivax CSP and overlapping peptides representing the variant repeats of the VK247 strain of P. vivax. We have demonstrated that the P. vivax CSP-specific antibody response is directed towards areas within the repeat region as well as areas external to this; but the dominant epitopes recognized by the two populations studied, were distinct. One epitope, lying external to the repeats and recognized by both populations, partially overlaps an area of the protein referred to as region II-plus. Sera from malaria-exposed Papua New Guineans and Thais contained antibodies to this epitope (V22, single letter amino acid sequence TCGVGVRVRRRVNAANKKPE) which were capable of recognizing sporozoites, as determined by quantitative inhibition IFA. Seventeen percent of PNG sera had antibodies to this peptide compared with 33% who had antibodies to the central repeats of the protein. Immunization of mice with recombinant CSP did not induce antibodies to V22. However, immunization with overlapping peptide epitopes representing this region (V21 or V22) induced specific antibodies but only two sera recognized both V21 and V22 and, by inference, the overlapping peptide sequence (TCGVGVRVRR). Antibodies in these two sera could bind recombinant CSP in ELISA; however, in contrast, nine sera which recognized either V21 or V22 alone did not bind CSP. Only one of two sera containing antibodies recognizing CSP stained P. vivax sporozoites. This serum also recognized an epitope dependent upon two amino acids aminoterminal to V22. These data suggest that the fine specificity of antibodies is a critical determinant for binding to both recCSP and sporozoites.

Adult

Implementation of the Patient Self-Determination Act: a survey of Nebraska hospitals.

The purpose of this survey of Nebraska hospitals (N = 79) was to describe the planning, implementation, and evaluation of the Patient Self-Determination Act (PSDA) and to explore the role of the nurse in these processes. Results indicate nurses were very involved in the planning phase but rarely in the implementing phase. Few evaluation strategies were utilized and only some respondents identified problematic issues related to the implementation of the PSDA. Clinical implications for issues related to the PSDA are discussed and framed within the American Nurses' Association Position Statement on the PSDA (1991). Future studies are suggested, especially related to evaluation of PSDA implementation.

American Nurses' Association

Onchocerca volvulus: identification and characterization of an immunogenic eggshell protein (Oveg1).

A major antigen recognized by human sera in Onchocerca volvulus infections is a parasite eggshell protein. The cDNA clone for this antigen was isolated from a lambda gt11 O. volvulus cDNA library using antisera from patients with high microfilarial counts. Sequence analysis of the cDNA clone predicts a polyglutamine repeat near the 5' end of the cDNA, and a motif of four arginines near the 3' end, reminiscent of that found in many regulatory proteins. The cDNA was subcloned into a yeast expression vector and reagent quantities of recombinant antigen produced in Saccharomyces cerevisiae. Antisera produced to the recombinant purified protein localized the antigen to the eggshell of developing microfilariae within the adult female uterus. No other sites of Oveg1 expression were noted in adult worms, but labeling was seen in internal membrane structures of L3 larvae. Sera from infected chimps recognized Oveg1 only after infections became patent. Sera from infected humans showed reactivity to Oveg1 that varied from 39 to 95%, depending upon the geographic location.

Amino Acid Sequence

Life-spans of human T-cell responses to determinants from the circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax.

The longevity of specific human memory T-cell responses is largely unknown. However, a knowledge of the duration of memory is important for understanding immunity to an organism and for planning vaccine intervention. To address this, we have examined T-cell memory to malaria by determining T-cell responses by subjects recently exposed to peptides spanning the circumsporozoite (CS) proteins of two species of malaria-causing organisms, Plasmodium falciparum and Plasmodium vivax. Responses to vivax CS peptides by exposed Thai subjects were more frequent than responses by nonexposed individuals, permitting identification of determinants seen by vivax-induced responses. At the population level, there appears to be life-long memory, as the time since individuals were exposed did not diminish responsiveness to these determinants. In contrast, falciparum-exposed subjects were largely indistinguishable from nonexposed controls in responsiveness to falciparum CS determinants. However, a single peptide (F16: DNEKLRKPKHKKLKQPGDGN) was recognized significantly more frequently by P. falciparum-exposed than nonexposed Thai subjects. T cells responsive to this peptide were CD450+ and produced gamma-interferon. In contrast to the response to the vivax determinants and the other falciparum determinants, responsiveness to F16 was undetectable or minimal 2 years after exposure. Our data provide the average life-spans of certain malaria-specific T cells and are consistent with, but do not prove, the hypothesis that antigenic persistence (in the form of P. vivax hypnozoites) correlates with persistence of human T-cell memory.

Adult

The effect of thymidine on the antibacterial and antiviral activity of zidovudine.

The effect of thymidine and deoxyadenosine on the antiviral and antibacterial effect of zidovudine was studied in human immunodeficiency virus type 1 (HIV-1) Escherichia coli and Salmonella typhimurium. In quantitative assays, 10 micrograms mL-1 thymidine was shown to increase the 50% inhibitory concentration (IC50) of zidovudine for HIV-1 by approximately 100-fold and to reduce zidovudine (1 microM)-induced protection of C8166 cells from 2.04 to 0.18 log syncytial-forming units. Thymidine also antagonized the antibacterial effect of zidovudine for two E. coli and three S. typhimurium species in a dose-dependent manner; 10 micrograms mL-1 of thymidine increased the minimum inhibitory concentration of zidovudine for E. coli strains by 10-40-fold and for S. typhimurium strains by three-fold. Deoxyadenosine reduced the minimum inhibitory concentration of zidovudine against all five bacterial strains but had no effect on the IC50 of zidovudine for HIV-1, nor did it significantly reverse the antagonism of the antibacterial and antiviral activity of thymidine. The induction of the SOS response in E. coli was reversed in a dose-dependent manner by thymidine while the presence of deoxyadenosine increased induction of the SOS response by zidovudine at suboptimal concentrations.

Deoxyadenosines

The use of dexamethasone in full-term infants with severe respiratory failure and pulmonary barotrauma.

Eight full-term infants (mean gestation 39.9 weeks [range 37-42] and mean birthweight 3642 g [range 3060-4200]) with severe respiratory failure (median oxygenation index 28 [range 16-65] and median arterial/alveolar PO2 ratio (a/APO2) 0.094 [range 0.038-0.165]) and pulmonary barotrauma were treated with Dexamethasone, 0.5 mg/kg per day, from the median age of 5 days (range 3-22). Six of the eight (75%) infants survived. They were weaned from mechanical ventilation and extubated a median of 2.5 days after commencing treatment with Dexamethasone. Two infants died and one of them suffered recurrent pneumothoraces. There was a significant improvement in oxygenation in the seven infants who survived the 72 h period of observation. Their median oxygenation index was 24 when Dexamethasone was commenced compared with 8 after 12 h (P less than 0.05) and 10 after 36 h (P less than 0.025). Their a/APO2 ratio was 0.095 when Dexamethasone was commenced compared with 0.289 after 12 h (P less than 0.05) and 0.207 after 36 h (P less than 0.025). There was a significant increase in the infants' arterial mean blood pressure associated with Dexamethasone therapy and one infant developed Staphylococcus aureus septicaemia. In this uncontrolled study of eight full-term infants with severe respiratory failure and pulmonary barotrauma, the use of Dexamethasone was associated with significant improvement in oxygenation and rapid weaning from mechanical ventilation.

Barotrauma

Cellular and humoral immune responses to a recombinant P. falciparum CS protein in sporozoite-immunized rodents and human volunteers.

The immune responses of sporozoite-immunized rodents and of human volunteers exposed to multiple bites of irradiated Plasmodium falciparum infected mosquitos have been investigated using a yeast-derived recombinant P. falciparum circumsporozoite (rPfCS) protein. The murine immune response to immunization with rPfCS was not genetically restricted. Nine different murine haplotypes, when immunized with rPfCS, developed high levels of antisporozoite antibodies detectable by IFA and RIA. In addition, injection of rPfCS induced a secondary antibody response in P. falciparum sporozoite-primed mice. Murine T-cell epitopes were mapped in the C terminus of the rPfCS protein using overlapping synthetic peptides. The human T-cell response was investigated using T-cell clones derived from peripheral blood lymphocytes (PBL) of a P. falciparum sporozoite-immunized volunteer. A total of 40 CD4+ T-cell clones were obtained. Stimulation indices ranged from 2.5 to 103.4 following challenge with rPfCS in the presence, but not in the absence, of antigen-presenting cells. The clones were specific for rPfCs and did not proliferate or secrete lymphokines when challenged with yeast-derived recombinant P. vivax or P. berghei CS protein or with a yeast-extract control. The clones also recognized the native CS protein in extracts of P. falciparum, but not P. berghei or P. cynomolgi, sporozoites.

Animals

Conserved repetitive epitope recognized by CD4+ clones from a malaria-immunized volunteer.

T cell clones obtained from a human volunteer immunized with Plasmodium falciparum sporozoites specifically recognized the native circumsporozoite (CS) antigen expressed on P. falciparum sporozoites, as well as bacteria- and yeast-derived recombinant falciparum CS proteins. The response of these CD4+ CD8- cells was species-specific, since the clones did not proliferate or secrete gamma interferon when challenged with sporozoites or recombinant CS proteins of other human, simian, or rodent malarias. The epitope recognized by the sporozoite-specific human T cell clones mapped to the 5' repeat region of the CS protein and was contained in the NANPNVDPNANP sequence.

Amino Acid Sequence

Cholinergic regulation of female sexual behavior in rats demonstrated by manipulation of endogenous acetylcholine.

Infusions of the cholinesterase inhibitor, eserine, into the lateral ventricle of the brain facilitated lordosis in ovariectomized, estrogen primed female rats. Lordosis was also facilitated by infusions of 5 or 10 micrograms acetylcholine when this was accompanied by a low dose of eserine. Systemic treatment with the muscarinic antagonist, atropine (2 mg), completely blocked the facilitative effects of eserine and acetylcholine. In female rats made highly receptive by treatment with estrogen and progesterone, lordosis was inhibited by infusion of scopolamine into the lateral ventricles. These results agree with previous findings that sexual receptivity is regulated in part by endogenous cholinergic activity.

Acetylcholine

Exchange lists: revised 1986.

A committee composed of members of The American Dietetic Association and the American Diabetes Association has revised Exchange List for Meal Planning. Changes were made, as deemed necessary, on the basis of nutritional recommendations for persons with diabetes as understood in 1986. Major changes include rewriting the text to make it more useful in the education of persons with diabetes; changing the order of the exchange lists to emphasize a high-carbohydrate, high-fiber diet, as well as to better reflect the order of foods in menu planning; adding symbols to foods high in fiber and sodium; changing nutritive values for the starch/bread and fruit lists; adding lists of combination foods, free foods, and foods recommended only for occasional use; developing a data base; and initiating a plan for field testing and evaluation. The committee also developed a simplified meal planning tool, Healthy Food Choices, to be used for initial or "survival" level education. In poster format, foods are grouped by calories into six food groups. Approximate portion sizes of commonly used foods are listed. Blank lines are provided for the nutrition counselor to write in a suggested menu or meal plan for the client. Because the booklet does not use the word "diabetes" specifically, it is appropriate as a general teaching tool.

Diabetes Mellitus

Dynamic process captured on a single image: an approach to screening for abnormal superior vena caval flow.

A strategy for displaying and archiving dynamic quantitative data from scintigraphic imaging is described and applied to diagnosing obstructed thoracic veins. A prospective series of 25 patients with concurrent radiographic contrast and tracer venograms along with 49 controls showed a 33% sensitivity, comparable to previously published data. The use of first harmonic Fourier analysis enhanced the screening value of the test by identifying all abnormals. Moreover, this format captured the dynamic physiologic data on a single photograph. This technique is readily available to nearly any nuclear imaging laboratory equipped with a gamma camera and a computer.

Computers