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Biomedical subjects

D Murphy

Publications and source records attributed to D Murphy.

At least 73 records · Page 4Linked to original sources

Combined lesions of hippocampus and subiculum Do not produce deficits in a nonspatial social olfactory memory task.

Rats transmit information to each other about which foods are safe to eat. If a rat smells a food odor on the breath of another rat, it is subsequently more likely to eat that food than an alternative. Work by Galef et al. (1988) has shown that the observer rat forms an association between two olfactory stimuli on the breath of the demonstrator rat that has eaten the food, the food odor and carbon disulphide, which is normally present in the rat breath. Bunsey and Eichenbaum (1995) claimed that the hippocampus/subicular region is required for the long-term retention of this nonspatial form of associative memory on the basis that combined lesions of the hippocampus and subiculum produced a deficit, but lesions of either structure alone did not. We report here a failure to repeat this finding. Rats with either combined lesions of the hippocampus and subiculum or with amygdala lesions were tested on their ability to remember this association either immediately (testing short-term memory) or after a 24 hr delay (testing long-term memory). Neither lesion group exhibited significant memory deficits on this nonspatial associative task at either test interval. In contrast, a deficit was observed on a spatial memory task (forced-choice alternation t-maze) for animals with combined lesions of the hippocampus and subiculum. These results contradict the findings of Bunsey and Eichenbaum (1995) and support the idea that the hippocampus/subicular region is not required for this nonspatial associative memory.

Amygdala↗

Sorting of the vasopressin prohormone into the regulated secretory pathway.

The sorting of soluble proteins into the regulated secretory pathway (RSP) involves aggregation, but whether an additional sorting domain is also required is not clear. By fusing vasopressin prohormone (proVP) fragments to green fluorescent protein (eGFP) we have determined whether a sorting domain can function independently of the aggregative neurophysin domain. Although eGFP itself can be immunolocalised in the RSP of Neuro2A and AtT20 cells, most of the protein enters the constitutive pathway, and is found in the culture medium. In contrast, the N-terminal 27 residues of proVP promote residence in the RSP. Furthermore, only the processed form of this fusion was secreted when stimulated. We suggest a sorting mechanism based on the recognition of a sorting motif, the efficiency of which is enhanced by neurophysin aggregation.

Animals↗

Pneumomediastinum, pneumothorax and subcutaneous emphysema complicating MIS herniorrhaphy.

PURPOSE: Videoscopic herniorrhaphy is being performed more frequently with advantages claimed over the conventional open approach. This clinical report describes a pneumothorax, pneumomediastinum and subcutaneous emphysema occurring at the end of an extraperitoneal videoscopic herniorrhaphy. CLINICAL FEATURES: A 25 yr old ASA I man presented for elective extraperitoneal videoscopic hernia repair. Following intravenous induction with fentanyl, midazolam and propofol a balanced anesthetic technique using enflurane in N2O and O2 was used. Apart from a prolonged operating time (195 min), the procedure and anesthetic was uneventful. At the conclusion of the operation, prior to reversal of neuromuscular blockade extensive subcutaneous emphysema was noted on removal of the surgical drapes. Chest radiography revealed a pneumomediastinum and pneumothorax. A 25 FG intercostal tube was inserted and connected to an underwater seal drain. Sedation and positive pressure ventilation was maintained overnight to permit resolution and avoid airway compromise. The clinical and radiological features had resolved by the next morning and the patient's trachea was extubated. His subsequent recovery was uneventful. CONCLUSION: Pneumothorax and pneumomediastinum are well recognised complications of laparoscopic techniques but have not been described following extraperitoneal herniorrhaphy. In this report we postulate possible mechanisms which may have contributed to their development, including inadvertent breach of the peritoneum and leakage of gas around the diaphragmatic herniae or tracking of gas retroperitoneally. The case alerts us to the possibility of this complication occurring in patients undergoing videoscopic herniorrhaphy.

Adult↗

Home bowel preparation for elective colonic procedures in children: cost savings with quality assurance and improvement.

BACKGROUND/PURPOSE: The current health care environment pressures providers to lower cost and demands quality care that is measured by outcomes and patient satisfaction. Most insurers will not approve bed days for in-hospital preoperative bowel preparations for elective colorectal procedures. This policy does not take into account that infants and children are unable to tolerate large volumes of enteral preparation, which adversely affects outcome because of an inadequate preparation. This report describes a prospective evaluation of a standard home bowel preparation regimen utilizing local and regional home health care agency support. METHODS: For an elective colorectal procedure, pediatric patients underwent a home bowel preparation using GoLYTELY (100 mL/kg) via a nasogastric tube infused over 4 hours by a pediatric home health nurse trained in this technique. During the bowel preparation, the nurse educated the family members about the service and performed physiological monitoring to insure safety. At the completion of the preparation, any unusual events were transmitted to the staff surgeon for further instructions. Our initial 30 patients were treated by our hospital home health agency personnel to insure safety. Since then, 41 additional bowel preparations have been performed by statewide agencies. RESULTS: Seventy-one patients underwent complete home bowel preparation (45 boys; 26 girls). The age range was 3 months to 9 years (average, 5 months). There was one complication caused by incorrect mixing of GoLYTELY causing gastrointestinal cramping. All 71 home bowel preparations were recorded as good at the time of the colorectal procedure by the staff pediatric surgeon. The average cost for home bowel preparation was $300 in network, and $350 out of network. This compares with an inpatient hospital day cost of greater than $800 ($36,000 savings). CONCLUSIONS: This technique offers the pediatric surgeon an opportunity to maintain a high standard of quality care while using home health agency personnel to minimize cost. This program is safe, effective, and associated with a good outcome and a high degree of family satisfaction.

Anus, Imperforate↗

Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons.

Functional chemokine receptors and chemokines are expressed by glial cells within the CNS, though relatively little is known about the patterns of neuronal chemokine receptor expression and function. We developed monoclonal antibodies to the CCR1, CCR2, CCR3, CCR6, CXCR2, CXCR3 and CXCR4 chemokine receptors to study their expression in human fetal neurons cultured from brain tissue as well as the clonally derived NT2.N human neuronal cell line (NTera 2/cl.D1). Specific monoclonal antibody labeling demonstrated expression of CCR2, CXCR2, CXCR3 and CXCR4 on neurons from both sources. Co-labeling studies revealed strong expression of CXCR3 and CXCR4 on both dendritic and axonal processes, with a weaker expression of CXCR2 and CCR2. Reverse transcriptase-polymerase chain reaction analysis of pure NT2.N neurons confirmed RNA expression for CCR2, CXCR2, CXCR3 and CXCR4. No changes in the neuronal labeling pattern of chemokine receptor expression were noted when NT2.N neurons were grown on a supporting layer of astrocytes, again consistent with similar patterns seen in primary human fetal brain cultures. Analysis of single-cell calcium transients revealed a robust response to stromal derived factor-1alpha (CXCR4) and melanocyte growth-stimulating activity (CXCR2), and variable response to monocyte chemoattractant protein-1 (CCR2) or interferon-gamma inducible protein-10 (CXCR3). Finally, we detected the release of monocyte chemoattractant protein-1 from pure cultures of NT2.N neurons, but not undifferentiated NT2 cells. These data indicate that individual neurons may not only co-express multiple functional chemokine receptors, but also that neurons themselves produce chemokines which may influence cellular function within the central nervous system.

Astrocytes↗

Differential regulation of adenosine A(1) and A(2A) receptors in serotonin transporter and monoamine oxidase A-deficient mice.

The serotonin (5HT) transporter (5HTT) removes 5HT from the synaptic cleft and is thus critical to the control of serotonergic neurotransmission. Mice with a targeted inactivation of the 5HTT represent a novel and unique tool to study serotonergic system functioning. Because the release of 5HT is regulated by adenosine, we investigated 5HTT-deficient mice for possible adaptive changes of adenosine A(1) and A(2A) receptors. A(1) and A(2A) receptors were studied by means of quantitative autoradiography using the radioligands [3H]8-cyclopentyl-1,3-dipropylxanthine and [3H]CGS 21680, respectively. A comparison of 5HTT knockout versus control mice revealed upregulation of A(1) receptors in the dorsal raphe nucleus (DRN, +21%), but not in any of the serotonergic projection areas, and downregulation of A(2A) receptors in basal ganglia. The adaptive changes of A(1) and A(2A) receptors in 5HTT-deficient mice are likely to represent a compensatory neuroprotective effect mediated by the adenosinergic modulatory system. For comparison, these receptors were also studied in monoamine oxidase A (MAOA) knockout mice and in 5HTT/MAOA double knockout mice. 5HTT/MAOA double knockout mice showed adaptive changes of adenosine A(1) and A(2A) receptors similar to 5HTT knockout mice, while investigation of MAOA-deficient mice revealed an upregulation of A(2A) receptors, which may relate to a role of both MAOA and adenosine A(2A) receptors in anxiety.

Animals↗

Laparoscopic surgical management of ectopic pregnancy: a district general hospital experience.

This is an audit of laparoscopic management of ectopic pregnancy in a District General Hospital (DGH), using a retrospective casenote review. The study was conducted at New Cross Hospital, Wolverhampton, a large DGH. We recorded the duration of operation, postoperative opiate requirement, length of hospital stay, operative and postoperative complications. Case notes of patients with surgically treated ectopic pregnancies between January 1996 and June 1998 (n=106) were reviewed and grouped into three categories: (1) immediate laparotomy, (2) laparoscopy followed by laparotomy, and (3) laparoscopic management. Comparisons were made between the three groups. The incidence of ectopic pregnancy was 1-91 live births. The mean age of the patients was 29.9 years (range 14-41). Seven (6.6%) patients were haemodynamically unstable and underwent immediate laparotomy, 66 (62%) patients had laparoscopic management while 33 (31%) patients had laparotomy following preliminary laparoscopy. Mean operative time in the laparoscopic management group was 61.9 minutes. The mean +/- 2 SD was 61.9+/-37.4 (range 27-107) with a mean length of hospital stay of 1.9 days (range 1-4), compared with 49.9 minutes (+/-SD 16.5 (range 35-98) and 3.9 days (range 2-8), respectively, in the laparotomy following preliminary laparoscopy group. Only one patient in the laparoscopic management group required opiate analgesia 24 hours postoperatively compared with all the patients in the immediate laparotomy group and seven patients (21%) in laparotomy following the preliminary laparoscopy group. Complications in the laparoscopic management group included wound infection and a persistent ectopic. One patient in the laparotomy group required subtotal hysterectomy for persistent bleeding from cornual ectopic, while complications in the laparotomy following the laparoscopy group consisted of minor wound infection and a case of deep venous thrombosis (DVT). Laparoscopic management of ectopic pregnancy is safe and can be carried out successfully in a DGH setting with clear advantages, including shorter hospital stay and reduced postoperative opiate requirement.

Journal Article↗

The development of a phantom to determine foetal organ doses from 131I in the foetal thyroid.

Iodine can accumulate in the foetal thyroid from the twelfth week of gestation onwards. If the iodine taken up by the foetal thyroid is in the form of 131I then the thyroid and its proximal tissues and organs will be irradiated. Several mathematical models exist in the literature on foetal/maternal iodine kinetics. However, very few studies have been performed where the foetal thyroid had been physically modelled thus allowing the determination of foetal organ dosimetry from 131I in the foetal thyroid. Here, the development of such a physical model or phantom is described and dosimetry results obtained from the phantom are discussed. The phantom is of Perspex construction, the dimensions of which are sufficient to incorporate models of the foetus at 16, 24 and 36 weeks' gestational age. The dosimetry of two organs is presented, that of the brain and the thymus. The results show that the measured absorbed dose is comparable with that calculated using modified MIRD dosimetry and traditional methods. The results also show that the dose to the thymus is greater than that of the brain by a factor of almost 30 for 16 weeks' gestational age.

Brain↗

Low-intensity physical activity benefits blood lipids and lipoproteins in older adults living at home.

OBJECTIVE: to examine the influence of low-intensity, habitual physical activity on blood lipids and lipoproteins and other cardiovascular risk factors in older adults living at home. DESIGN: cross-sectional observational study. PARTICIPANTS: a convenience sample of healthy, older adults (n = 155) who were mainly non-Hispanic, white (96.8%), female (65.2%) and on medications for cardiometabolic-related disorders (60.6%) and had an average age of 74.2 +/- 0.5 years. METHODS: we used a question from the Yale Physical Activity Survey to assess the typical number of hours per day spent in motion during the past month, collapsing responses into <5 and > or = 5 h/day. We determined blood lipids, lipoproteins and glucose with Kodak Ektachem serum oxidase assays or finger stick using the Cholestech LDX system enzymatic technique, and measured blood pressure by auscultation. Waist circumference was the indicator of abdominal fat distribution and body mass index the measure of overall adiposity. RESULTS: after adjusting for age, sex, adiposity, postprandial state, medication use and method of blood sampling, greater amounts of daily accumulated movement were associated with more favourable blood lipid-lipoprotein profiles. Subjects reporting > or = 5 h of daily movement had higher levels of high-density lipoprotein cholesterol [mean difference (95% confidence interval): 0.23 mmol/l (0.07, 0.39); P = 0.002] and a lower ratio of total to high-density lipoprotein cholesterol [average difference: -0.92 (-1.36, -0.48); P = 0.003]. They had lower levels of low-density lipoprotein cholesterol [mean difference: -0.39 mmol/l (-0.80, 0.03); P = 0.074)] and a lower ratio of triglyceride to high-density lipoprotein cholesterol [mean difference: -1.31 (-2.50, -0.12); P = 0.059]. Total cholesterol was similar in the two groups (P > 0.05). The mean blood glucose was 1.49 mmol/l lower (-2.67, -0.31) in the more active group (P = 0.02), independent of age, sex, adiposity, medication use and postprandial state. CONCLUSIONS: low-intensity, habitual physical activity is a sufficient stimulus to enhance blood lipids/lipoproteins and glucose in older adults, independent of abdominal and overall adiposity.

Age Factors↗

Molecular misreading in non-neuronal cells.

+1 Frame-shifted proteins such as amyloid precursor protein(+1) and ubiquitin-B(+1) have been identified in the neuropathological hallmarks of Alzheimer's disease. These frameshifts are caused by dinucleotide deletions in GAGAG motifs of messenger RNA encoded by genes that have maintained the unchanged wild-type DNA sequence. This process is termed 'molecular misreading'. A key question is whether this process is confined to neurons or whether it could also occur in non-neuronal cells. A transgenic mouse line (MV-B) carrying multiple copies of a rat vasopressin minigene as a reporter driven by the MMTV-LTR promotor was used to screen non-neuronal tissues for molecular misreading by means of detection of the rat vasopressin(+1) protein and mutated mRNA. Molecular misreading was demonstrated to occur in several organs (e.g., epididymis and the parotid gland) where transgenic vasopressin expression is abundant, but its penetrance is variable both between and within tissues. This implies that non-neural tissues too, could be affected by cellular derangements caused by molecular misreading.

Animals↗

Gene transfer strategies for the physiologist.

Foreign genes can be introduced into whole animals using methods of germline transgenesis and somatic gene delivery. While germline transgenesis can generate useful animal models for genetic studies, it can be costly, time-consuming and requires the use of a large number of animals. An alternative means of gene transfer is to deliver genes to somatic cells using non-viral and viral technologies. Non-viral methods such as naked DNA injection, electroporation and liposome/cation lipid-mediated gene transfer are relatively inefficient. In contrast, viruses are effective vehicles that carry foreign genes into a cell rapidly and efficiently. Here we illustrate the usefulness of adenoviral vectors to express a potent and specific inhibitor of cAMP-dependent protein kinase (PKA) to study the role of cyclic 3',5'-cyclic AMP (cAMP) in the osmotic regulation of the vasopressin gene in a transgenic rat model. The ability to modify endogenous systems within specific cells in a whole animal model allows gene effects to be studied with physiological relevance. The combination of molecular biology and integrative physiology is a powerful application that can aid in the elucidation of how gene function can translate into complex systems in an organism.

Adenoviridae↗

Transgenic studies in rats and mice on the osmotic regulation of vasopressin gene expression.

Over the past 10-15 years, profoundly important transgenic techniques have been developed that enable new genes to be introduced into whole mammalian organisms. This review describes the ways in which transgenic animals, both rats and mice, have been used to study the mechanisms by which the expression of the vasopressin gene is confined to specific neurones in the hypothalamus, and how the pattern of that expression is altered following an osmotic challenge to the organism.

Animals↗

An exploration of the concept of loneliness in forensic psychiatry.

Subjective aspects of social support and loneliness were examined in a group of 30 forensic inpatients in secure units and were compared to a control group of 31 surgical inpatients. The secure-unit patients were more lonely and experienced the deficiencies in their social relationships in a different way to the controls. Loneliness for the secure-unit patients was a more unpleasant experience and more associated with difficulties in forming close attachments. There was a high correlation between loneliness and the personality trait of psychoticism in the secure-unit group which was not found in the controls. These results underline the serious problems of these patients with relationships and suggest the development of intervention programmes.

Forensic Psychiatry↗

Thyroid dosimetry in Europe following the Chernobyl accident.

Thyroid dose estimates for European populations following the Chernobyl accident in 1986 have been presented in the literature. These dose estimates used standard values for parameters such as thyroid mass, iodine uptake and biological half-life. Previous work has shown that these values are not representative of European populations and that local values should be utilized. Using published data on revised thyroid dose estimates, thyroid dosimetry data arising as a result of the Chernobyl accident are presented for 22 European countries. When these are compared with previously published estimates it is found that in all cases the previous results underestimate the thyroid dose by up to a factor of 4. Risk estimates on the incidence of fatal and non-fatal thyroid cancers are also determined from this new data and, again, the results are underestimated. The results show an increase in the number of fatal cancers, rising from 149 as predicted by the NEA to 310 under the new estimates, and from 180 as predicted by UNSCEAR to the new estimate of 380.

Adult↗

Effects of composite thickness on the shear bond strength to dentin.

The manufacturers of some condensable posterior composites claim that their products can be placed in bulk and light-cured in 5-mm-thick increments. This study compared the shear bond strengths of three composite resins when bonded to dentin in 2- and 5-mm-thick increments. Overall the bond strengths were adversely affected by the composite thickness (p < 0.0001). The shear bond strength of each composite tested was much lower when polymerized in a 5-mm increment than in a 2-mm increment of composite (p < or = 0.0005). The two condensable composites tested had a lower bond strength than the conventional composite when polymerized in a 5-mm bulk increment (p < or = 0.01).

Analysis of Variance↗