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Biomedical subjects

J R Murphy

Publications and source records attributed to J R Murphy.

288 records · Page 16Linked to original sources
PubMed1968

Hemoglobin CC disease: rheological properties or erythrocytes and abnormalities in cell water.

Suspensions of erythrocytes from patients with hemoglobin (Hb) CC disease showed an increased viscosity and decreased filterability suggesting a less deformable cell. Hemolysates prepared from Hb CC erythrocytes had an increased viscosity compared with hemolysates of normal cells, suggesting that the increased viscosity of Hb CC cells in serum was the result of an increased internal viscosity of the cell. These abnormal rheological properties of Hb CC erythrocytes were associated with a decreased content of cations and an abnormality of cell water. The fraction of the cell volume, which is water in Hb CC cells, was 95.5% of normal. The amount of cell water in Hb CC cells available for osmotic equilibrium, termed solvent water, was only 67% of that in normal cells. The smaller amount of solvent water in Hb CC cells indicates a greater amount of water bound to protein. Altered rheological properties of erythrocytes with Hb AA, CC, and SC also were observed during pregnancy. Suspensions of erythrocytes in serum or plasma from pregnant patients resulted in an increased viscosity compared with suspension in serum or plasma from nonpregnant individuals. An increased viscosity during pregnancy is consistent with the increased severity of the hemolytic anemia in patients with these hemoglobinopathies during pregnancy. The studies reported here suggest that in Hb CC disease the mechanism of erythrocyte destruction, splenic sequestration, results from the increased viscosity, and less deformability of the erythrocyte with on increased internal viscosity.

Alkanes↗
PubMedDate not supplied

Estimate of anti-Plasmodium falciparum sporozoite activity in humans vaccinated with synthetic circumsporozoite protein (NANP)3.

A mathematical model was defined to estimate the degree of in vivo activity against Plasmodium falciparum sporozoites expressed by volunteers vaccinated with a synthetic peptide comprising the immunodominant epitope of the circumsporozoite protein. Relative to the course of infection in non-immunized controls, infections in vaccinated volunteers corresponded to the neutralization or delay of development of greater than 99% of challenge sporozoites.

Animals↗
PubMedDate not supplied

The first-night effect may last more than one night.

The first-night effect in sleep polysomnographic studies is usually considered to last for one night. However, a few observations have indicated that variables associated to rapid eye movement sleep take longer to stabilize. Notwithstanding, current opinion holds that second nights of recording can be used without restriction for research and clinical purposes. The goal of this study was to describe the dynamics of habituation to polysomnography in optimal conditions. Twenty-six young, carefully screened, healthy subjects were recorded in their home for four consecutive full polysomnographies. Repeated measures ANOVA were applied. Between the two first nights, while there were no differences in sleep duration in non-rapid eye movement sleep, marked modifications in corresponding spectral power were observed. The dynamics of adaptation of rapid eye movement sleep appeared to be a process extending up to the fourth night. Similar dynamics in NREMS and REMS homeostasis have been observed in sleep deprivation studies, and it appears that the same mechanisms may be responsible for the FNE. The longer habituation process of REMS in particular has important implications for sleep research in psychiatry.

Adolescent↗
PubMedDate not supplied

Critical analysis of the theories advanced to explain short REM sleep latencies and other sleep anomalies in several psychiatric conditions.

One of the most consistent and most studied sleep modifications in several psychiatric conditions is the shortening of the rapid eye movement (REM) sleep latency. While its clinical usefulness is still to be proven and its meaning relatively obscure, the appearance of a short REM latency continues to be a daily fact in sleep laboratories. Many theories compete to explain what is observed, the most important being the circadian rhythm hypotheses, the homeostatic model and the reciprocal interaction model. These three are summarised and their pros and cons are exposed in a systematic manner. Points of conflict, possible convergences and limitations are discussed in the light of recent developments on the general theories of sleep regulation.

Body Temperature↗
PubMedDate not supplied

Interleukin 7 (IL-7) receptor-specific cell killing by DAB389 IL-7: a novel agent for the elimination of IL-7 receptor positive cells.

Interleukin 7 (IL-7) induces the proliferation of B cell progenitors in long-term bone marrow cultures, promotes the growth of resting fetal and adult thymocytes, and costimulates mature human T cell proliferation. IL-7 also induces cell growth in hematologic malignancies such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, and Sezary syndrome. We have constructed a recombinant fusion protein, DAB389 IL-7, composed of the catalytic and transmembrane domains of diphtheria toxin (DT), fused to IL-7. We demonstrate that DAB389 IL-7 is selectively cytotoxic for only those cells bearing the IL-7 receptor and that entry into target cells is mediated through the receptor. The nontoxic mutant, DA(E149S)B389 IL-7, was constructed and used to demonstrate that the catalytic domain of DT is responsible for the ADP ribosylation of elongation factor 2 that results in cytotoxicity. Finally, we demonstrate that DA(E149S)B389 IL-7 induces the growth of IL-7-dependent cells, verifying the bioactivity of the IL-7 binding domain of DAB389 IL-7. We propose that DAB389 IL-7 may be an important reagent in studying the IL-7--IL-7 receptor complex and may possess potential as a therapeutic agent against IL-7 receptor-bearing hematologic malignancies.

Adenosine Diphosphate Ribose↗
PubMedDate not supplied

Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites.

A 12 amino-acid synthetic peptide (NANP)3 comprising the immunodominant epitope of Plasmodium falciparum circumsporozoite protein was conjugated to tetanus toxoid (TT), adjuvanted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. No significant adverse reactions were noted, with mild soreness at the injection site the only common symptom. Seroconversions against NANP occurred in 53% and 71% of recipients of 100 or 160 micrograms, respectively, measured by enzyme-linked immunosorbent assay (ELISA). Most ELISA-positive sera reacted with sporozoites by indirect immunofluorescence (IFA). Three vaccinees with the highest ELISA and IFA titres and four unimmunized controls were challenged with P. falciparum sporozoites introduced via the bites of infective Anopheles mosquitoes. Blood stage parasites were detected in all controls by 10 days (mean 8.5 days, range 7-10). In contrast, the two vaccinees who became infected did not manifest parasitaemia until day 11 and the third vacinee showed neither parasites nor symptoms during the 29 day observation period. This first synthetic peptide parenteral vaccine against a communicable disease tested in man is safe and stimulates biologically active antibodies. These observations encourage the development of improved vaccine formulations which, by enhancing immunogenicity, may lead to practical vaccines to assist in the control of falciparum malaria.

Animals↗
PubMedDate not supplied

The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations.

Five hundred episodes of septicemia were reviewed, with emphasis on laboratory and epidemiologic findings. The isolation of facultative and anaerobic gram-negative bacilli, fungi, and gram-positive cocci (except viridans streptococci and Staphylococcus epidermidis) almost always indicated true bacteremia, whereas the isolation of aerobic and anaerobic gram-positive bacilli, including Clostridium species, often represented contamination. More than 99% of all episodes were detected when two samples of blood (a total of 30 ml) were cultured. The five most common isolates were Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The incidence of septicemia was highest among medical patients and lowest among obstetric-gynecologic patients. Two-thirds of all episodes were nosocomial; S. aureus, enterococci, facultative gram-negative bacilli, and fungi were especially common nosocomial pathogens. The microorganisms isolated varied with the hospital service; polymicrobial episodes were especially common among surgical patients and transplant recipients. The most common sources of bacteremia were the respiratory, genitourinary, and gastrointestinal tracts; however, the source was unknown in nearly one-third of episodes. Microorganisms causing septicemia in neutropenic and nonneutropenic patients were not different; however, polymicrobial infections were more frequent in the presence of neutropenia. After antimicrobial susceptibility data became available, therapy was appropriate greater than 90% of the time.

Bacteria↗
PubMedDate not supplied

The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. II. Clinical observations, with special reference to factors influencing prognosis.

Among 500 patients with bacteremia and fungemia, total mortality was 42%; about half of all deaths were attributable directly to infection. Mortality increased with age, but deaths unrelated to infection itself were responsible in part for this increase. Mortality was 2.6% among obstetric-gynecologic patients, 42% among medical patients, 49% among surgical patients, and 60% among transplant patients. The risk of death was especially high with enterococcal, facultative gram-negative, fungal, polymicrobial, or hospital-acquired sepsis; in the presence of shock, leukopenia, absolute granulocytopenia, or defined predisposing conditions (neoplasia, cirrhosis, and combinations of factors such as surgery and renal failure); and with a primary infected focus in the respiratory tract, the skin, a surgical wound, an abscess, or an unknown site. Body temperature was inversely related to mortality. Survival was increased by the use of appropriate antibiotics and, where applicable, additional therapeutic maneuvers (e.g., drainage). Multivariate analysis defined seven variables that independently influenced outcome: microorganism, blood pressure, body temperature, primary focus of infection, place of acquisition of infection, age, and predisposing factors. Although some adverse prognostic factors are not amenable to intervention, prevention of nosocomial bacteremia and fungemia and early reversal of hypotension may reduce the death rate from sepsis.

Adolescent↗
PubMedDate not supplied

Evaluation of an intervention to change benzodiazepine-prescribing behavior in a prepaid group practice setting.

To determine the effect of two levels of educational intervention on benzodiazepine-prescribing behavior in an elderly population in a controlled prepaid group practice (PPGP) setting, we designed a prospective controlled trial, with six-month follow-up. Our setting was a 270,000 member group-model PPGP in Colorado, from 1990 to 1991. Participants included 91 physicians, 62 men and 29 women; median age was 38.7 years. Group 1 received a one-on-one educational presentation by a clinical pharmacist, written educational materials, a brief follow-up visit, and feedback with recommendations. Group 2 received only a face-to-face presentation, given to departmental groups, as well as the same written educational materials used in group 1. Controls received no intervention. Our primary outcome measure was the benzodiazepine "on/off" status of the elderly PPGP members. The secondary outcome measure was the median change (preintervention minus postintervention) in a standardized amount of benzodiazepines prescribed per physician. Logistic regression analysis failed to show a significant effect on postintervention benzodiazepine on/off status between study groups, when controlling for preintervention on/off status, PPGP-member age, PPGP-member gender, and all possible interactions. Analysis of variance failed to demonstrate an effect of either intervention on the median change in standardized amount of benzodiazepines prescribed per physician, with groups 1, 2, and controls yielding values of -278 (range: -4,137, 2,844), -330 (-1,531, 1,358), and -541 (range: -3,716, 2,185), respectively. We conclude that strategies effective in changing physician prescribing behavior in other settings may not be effective in a PPGP setting with benzodiazepines in the elderly as the target for change.

Adult↗