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Biomedical subjects

J A Murphy

Publications and source records attributed to J A Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Target-derived neurotrophins may influence the survival of adult retinal ganglion cells when local neurotrophic support is disrupted: Implications for glaucoma.

Following target innervation, developing and neonatal retinal ganglion cells (RGCs) depend on neurotrophic factors from their target tissue for survival. This dependence is reduced for adult RGCs which rely primarily on trophic support from their local environment; however, some findings indicate that target tissue may play a role in the long-term survival of RGCs. We propose that a deficiency in neurotrophic factors from the target tissue may influence the survival of RGCs when local neurotrophic support is disrupted. Furthermore, we propose that this hypothesis may explain, at least in part, the progressive loss of RGCs in optic neuropathies such as glaucoma. Neurotrophic factors are present in the adult superior colliculus and they are trafficked to the retina; however, removal or lesioning of the adult target tissue results in little or no RGC loss for up to several months. In vitro, adult RGCs will survive when maintained by co-culturing these neurons with their target tissue. As well, the timing and pattern of adult RGC loss is consistent with that seen in glaucoma and in reports of delayed RGC loss following target-removal. Our hypothesis can be tested by selectively disrupting local neurotrophic support and evaluating RGC survival when target-derived neurotrophic support is maintained and when it is disrupted. Specifically, intravitreal injection of blocking antibodies could be used to disrupt local neurotrophic signaling, while aspiration of the superior colliculus will eliminate retrograde transport from the primary target tissue in rodents. The results of these experiments would provide valuable information concerning the influence of target-derived neurotrophic support when local neurotrophin signaling is disrupted. Specifically, this research could verify whether deficiencies in target-derived neurotrophic support play a role in RGC loss during glaucoma. A further understanding of this mechanism may lead to the development of effective neuroprotective strategies for treating glaucoma.

Adult↗
PubMed2005

Azide rearrangements in electron-deficient systems.

The azide group has a diverse and extensive role in organic chemistry, reflected in the power of azide anion as a strong nucleophile, the role of organic azides as excellent substrates for cycloaddition reactions, the uses of azides as precursors of amines and nitrenes, and azide rearrangements known as the Curtius and Schmidt reactions. In recent years the scope of the Schmidt reaction has begun to be explored in depth, so that it now represents an important reaction in synthetic chemistry. This tutorial review analyses and summarises key recent developments in the field of Schmidt reactions.

Alcohols↗
PubMed2005

Mechanisms of acinar cell injury in acute pancreatitis.

Acute pancreatitis has many causes, all leading to a common pathway of changes within the pancreatic acinar cell. Key amongst these changes is premature intracellular activation of digestive enzymes but this is also accompanied by the appearance of cytosolic vacuoles, co-localization of digestive and lysosomal enzymes, activation of NF-kappaB, and release of pro-inflammatory cytokines. The exact mechanism responsible for enzyme activation remains the subject of much research effort and not a little debate, however it is clear that all of these changes are triggered by an abnormal, sustained rise in cytosolic calcium concentration, which is itself dependent both on release of calcium from endoplasmic reticulum stores and uptake from the extracellular milieu. Activated enzymes are directly damaging to the acinar cell themselves, but recruitment of circulating neutrophils leads to further cellular damage. Cytokines and neutrophil activation are also responsible for the systemic inflammatory response typically seen in severe acute pancreatitis.

Acute Disease↗
PubMed2003

Stimulant doses of caffeine induce c-FOS activation in orexin/hypocretin-containing neurons in rat.

Although caffeine is a commonly used CNS stimulant, neuronal mechanisms underlying its stimulatory effect are not fully understood. Orexin (hypocretin)-containing neurons play a critical role in arousal and might be activated by acute administration of caffeine. We examined this possibility by using dual-immunostaining for orexin B and c-Fos protein as a marker for neuronal activation. Rats were administered intraperitoneally with 10, 30 or 75 mg/kg caffeine, or saline. As previously reported, caffeine increased locomotion at 10 and 30 mg/kg, but not at 75 mg/kg. The numbers of orexin-immunoreactive and non-orexin-immunoreactive neurons expressing c-Fos were analysed using three counting boxes within the orexin field in the posterior hypothalamus. Compared with saline, all doses of caffeine increased the number of cells immunoreactive for both orexin and c-Fos. The average magnitude of this increase across doses in orexin neurons differed amongst regions; c-Fos expression increased by 343% in the perifornical area and by 158% in the more medial, dorsomedial nucleus. In the lateral hypothalamic area, c-Fos expression increased by 226% at 10 and 30 mg/kg but no change was seen at 75 mg/kg. In contrast, caffeine significantly increased the number of non-orexin-immunoreactive neurons expressing c-Fos only in the dorsomedial nucleus. These results indicate that systemically administered caffeine preferentially activates orexin neurons over non-orexin neurons in the same field, and that this activation is most pronounced in the perifornical region where orexin neurons are most concentrated. The activation of orexin neurons might play a role in the behavioural activation by caffeine.

Animals↗
PubMed2001

1,4-pentadienyl-3-sulfonamides: frameworks for "disfavored" radical cascade cyclizations.

[reaction: see text]. 1,4-pentadienyl-3-sulfonamides afford products including those resulting from disfavored 5-endo-trig reactions when subjected to radical cyclization conditions. Products resulting from pathways featuring 4-exo-trig cyclizations are also detected, even when the 4-exo-trig reaction leads to a highly strained bicyclo[3.2.0] ring system.

Alkadienes↗
PubMed2001

Bispectral index monitoring in children undergoing mild hypothermic cardiopulmonary bypass.

BACKGROUND: In this prospective, cohort study of 15 children (median age 7.7 years, range 4.9-16.5 years) undergoing atrial septal defect repair, we evaluated changes in the Bispectral index (BIS) as a potential monitor of level of consciousness during cardiac anaesthesia. METHODS: Identical cardiac surgery, cardiopulmonary bypass (CPB) and anaesthetic techniques were used, including mild hypothermia and an early extubation protocol. BIS, mean arterial pressure, heart rate and tympanic temperature were recorded at baseline postinduction (Tbaseline), skin incision (Tincis), sternotomy (Tsternot), aortic cannulation (Tcann), nadir temperature (Tnadir), rewarmed (Trewarmed), immediate post-CPB (TpostCPB), chest drain insertion (Tdrains), sternal wires (Twire), skin closure (Tclosed) and spontaneous movement (Tmove). As a measure of stress response, serum lactate, glucose, norepinephrine and epinephrine levels were measured at Tbaseline, Tsternot, Tcann, Tnadir, Trewarmed and Tdrains. Explicit memory testing was undertaken prior to hospital discharge. RESULTS: BIS increased significantly during the rewarming phase (Trewarmed versus Tbaseline and Tnadir, P<0.001). Lactate, epinephrine and glucose levels were also significantly elevated at Trewarmed. There were no correlations between BIS and the increase in epinephrine, lactate and glucose during rewarming, nor with changes in heart rate or mean arterial pressure during surgery. All patients had an uneventful recovery without evidence for explicit recall. CONCLUSIONS: The increase in BIS during the rewarming phase could reflect an increase in conscious level, and is consistent with the reported risk for awareness during this phase of cardiac surgery.

Adolescent↗
PubMed2001

Low-dose versus high-dose heparinization during arteriovenous carbon dioxide removal.

The purpose of this study was to compare low-dose (LD) and high-dose (HD) systemic heparinization in a prospective randomized study of arteriovenous carbon dioxide removal (AVCO2R) during acute respiratory distress syndrome, using a commercially available heparin-coated oxygenator. Adult sheep (n = 13) received an LD50 smoke inhalation and 40% TBSA third degree cutaneous flame burn injury. At 40-48 h post-injury, animals underwent cannulation of the carotid artery and jugular vein and were then randomized to HD heparin (activated clotting time, ACT > 300s, n = 6) and LD heparin (ACT < 200s, n =7) and placed on AVCO2R for approximately 72 h using an oxygenator with the Trillium Bio-Passive Surface. Mean ACTs were significantly different, as expected (HD: 446 +/- 26s, LD: 213 +/- 12s, p < 0.05). AVCO2R shunt flow averaged approximately 13% of cardiac output with mean CO2 removal similar in HD and LD, p = NS. The hematocrit, platelet count, and fibrin degradation products for the two groups were not different. No differences in thrombosis or bleeding were noted. In conclusion, LD systemic heparin (ACT < 200s) with a heparin-coated oxygenator does not increase thrombogenicity during AVCO2R for smoke/burn-induced severe lung injury in sheep.

Acute Disease↗
PubMed2000

Epidural analgesia for cephalic version: a randomized trial.

OBJECTIVE: To determine if epidural analgesia improves the success rate of external cephalic version. METHODS: Women with singleton fetuses in breech or transverse presentation of at least 37 weeks' gestation were offered enrollment in a randomized trial. Inclusion criteria included maternal age of 18 years or older, nonvertex presentation confirmed by ultrasound, intact membranes, reactive fetal nonstress test, and estimated fetal weight (EFW) between 2000 and 4000 g. Women in the epidural group had lumbar epidural catheters inserted, through which 2% lidocaine and 100 microg of fentanyl were infused. External cephalic version attempts were done with ultrasound guidance in a standard fashion for both groups. The primary outcome variable was the successful version of the fetus to a cephalic presentation. RESULTS: There were no statistically significant differences between groups in gestation at time of procedure, placental location, fetal lie, gravity, parity, EFW, or amniotic fluid index. External cephalic version was successful in 32 of 54 women (59%) with epidural anesthesia compared with 18 of 54 (33%) with no anesthesia (relative risk [RR] 1.8, 95% confidence interval [CI] 1.2, 2.8, P <.05). Vaginal delivery occurred in 29 of 54 women (54%) in the epidural group and 16 of 54 women (30%) in the control group (RR 1.9, 95% CI 1.2, 2.9, P <.05). CONCLUSION: Epidural analgesia increased the success rate of external cephalic version and the likelihood of subsequent vaginal delivery.

Adult↗
PubMed2000

Fungal surveillance of an open haematology ward.

Air sampling and surveillance cultures for fungi were performed in a Scottish general haematology ward over a five-month period in 1997. The mean total fungal count from the air sampling appeared to be correlated with the number of patients colonized by Aspergillus. The most commonly isolated species were Aspergillus versicolor, A. fumigatus and A. niger. Rooms with portable air filtration units had significantly lower total fungal counts than the others. Swabs were taken from 70 patients (mean age 62 years); 114 of the 563 cultures (20.2%) were positive. The most commonly isolated species were A. fumigatus, Candida albicans, C. glabrata and C. parapsilosis. Samples taken from the tongue and perineum showed colonization more often than those taken from the nostrils. Almost half the patients (48.6%) were colonized on, or within seven days of, admission; 11.4% became colonized whilst on the unit. One patient developed fatal aspergillosis. We conclude that colonization or high air-borne spore concentrations are not necessarily predictive of fungal infection but may prompt early treatment or more aggressive prophylaxis of potentially fatal invasive infections.

Adolescent↗
PubMed1998

Double pessary use in grade 4 uterine and vaginal prolapse.

BACKGROUND: Certain situations dictate conservative management of grade 4 uterine or vaginal vault prolapse in women. The reduction of a prolapse may not be possible if the vagina cannot retain a single pessary. We have used double pessaries in the management of this condition. TECHNIQUE: With the patient in the dorsal lithotomy position, either a Donut or Inflatoball (Milex Products Inc., Chicago, IL) pessary is inserted and pushed into the vagina as far as is comfortable. A second pessary, either a flexible Gellhorn or Shaatz (Milex Products Inc.), then is placed caudad to the first. EXPERIENCE: We have used this approach in five women who have been followed for 7-15 months. There have been no erosions or vaginitis and all the women experienced symptomatic relief. CONCLUSION: In women who want or require conservative management of grade 4 prolapse and are unable to retain a single pessary, the placement of two pessaries often will be successful.

Aged↗
PubMed1998

Target tissues affect cellular properties of cocultured leech Retzius neurons.

The development of many neurons, including the Retzius (Rz) neurons of the medicinal leech, is shaped in part by interactions with other cells in the environment. To explore the nature of the interaction between growing Rz processes and potential target tissues, adult Rz neurons were cultured directly in contact with some of the tissues that normally serve as their targets in vivo. The morphology of the regenerated processes of these neurons varied depending upon the identity of the target tissues, but other cellular properties remained unchanged. In particular, although during normal development contact with peripheral targets determines the sign of Rz neurons' response to acetylcholine (ACh) applied to the soma, these cultured neurons maintained their original response to ACh even after as long as 2 weeks in culture on novel targets. Hence, some features of cultured adult Rz neurons varied depending upon the conditions, whereas other features remained fixed.

Acetylcholine↗
PubMed1997

Nursing process redesign with the implementation of a computer based patient record in the ambulatory setting.

Increasingly, health care organizations are considering moving to Computer Based Patient Records (CPR), a trend driven by managed care and capitated payments. Central to the change is recognition of the need for community based and clinically relevant information systems that span the care continuum. Thus, Aurora Health Care chose to start their CPR effort in the ambulatory setting as the focus of health care delivery in the evolving paradigm. This paper describes computerization of the ambulatory record in a 45 physician clinic and associated workflow redesign. Months were spent in the processes of: current state documentation and analysis, future state design, detail system design, and workflow reengineering. There was substantial impact on nursing care delivery with computer system interaction at the point of care in the exam room. Access to clinically relevant longitudinal data was found key to the implementation and evaluation of Care Management strategies.

Ambulatory Care Facilities↗
PubMed1997

Summary of measured radiofrequency electric and magnetic fields (10 kHz to 30 GHz) in the general and work environment.

We have plotted data from a number of studies on the range of radiofrequency (RF) field levels associated with a variety of environmental and occupational sources. Field intensity is shown in units of volts/meter (V/m) for electric field strength and amps/meter (A/m) for magnetic field strength. Duty factors, modulation frequencies, and modulation indices are also reported for some sources. This paper is organized into seven sections, each cataloging sources into appropriate RF frequency bands from very-low frequency (VLF) to super-high frequency (SHF), and covers frequencies from 10 kHz to 30 GHz. Sources included in this summary are the following: Coast Guard navigational transmitters, a Navy VLF transmitter, computer visual display terminals (VDTs), induction stoves or range tops, industrial induction and dielectric heaters, radio and television broadcast transmitters, amateur and citizens band (CB) transmitters, medical diathermy and electrosurgical units, mobile and handheld transmitters, cordless and cellular telephones, microwave ovens, microwave terrestrial relay and satellite uplinks, and police, air traffic, and aircraft onboard radars. For the sources included in this summary, the strongest fields are found near industrial induction and dielectric heaters, and close to the radiating elements or transmitter leads of high power antenna systems. Handheld transmitters can produce near fields of about 500 V/m at the antenna. Fields in the general urban environment are principally associated with radio and TV broadcast services and measure about 0.1 V/m root-mean-square (rms). Peak fields from air traffic radars sampled in one urban environment were about 10 V/m, 300 times greater than the rms value of 0.03 V/m when the duty factor associated with antenna rotation and pulsing are factored in.

Electromagnetic Fields↗
PubMed1996

Iron overload and liver dysfunction after allogeneic or autologous bone marrow transplantation.

Patients who require a bone marrow transplant (BMT) for leukaemia, lymphoma or other haematological disorders receive large quantities of blood products, including red cell concentrates, during the transplant period. Many receive red cell transfusions as part of treatment prior to BMT, adding to the potential iron load. However, organ dysfunction as a consequence of the transfused iron load would be surprising given the amounts of iron transfused. We studied 76 survivors of allogeneic and autologous BMT who were at least 1 year post-transplant and found that the majority (88%) had raised ferritins. Impaired liver function was common in these patients and in half was unexplained by viral hepatitis, veno-occlusive disease or graft-versus-host disease (GVHD), suggesting that iron overload may be an important contributing factor to liver disease in the stable post-transplant setting. This view is supported by the observation of improving liver function tests in 10 patients after a trial of venesection therapy.

Adolescent↗