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Biomedical subjects

A Murphy

Publications and source records attributed to A Murphy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Molecular and clinical characteristics in 32 families affected with familial adenomatous polyposis.

Germ-line mutations in the 5' half of the Adenomatous Polyposis Coli (APC) gene are found in about 80% of the patients affected with familial adenomatous polyposis (FAP). The vast majority of these are nonsense or frameshift mutations which result in the loss of the carboxyl terminus of the APC protein. Using an in vivo assay in yeast, we have identified pathogenic germ-line mutations in 26 of 32 (81%) unrelated Swiss families affected with FAP. Nine mutations were novel and eight families were shown to harbor two recurrent mutations. Correlations were attempted between the location of APC germ-line mutations and clinical manifestations of the disease.

Adenomatous Polyposis Coli↗
PubMed2001

Characterization of secondary hyperalgesia produced by topical capsaicin jelly--a new experimental tool for pain research.

Peripheral administration of the nociceptive agent capsaicin is used as an experimental tool to study neurophysiological and pharmacological aspects of the generation and control of pain. When investigating secondary hyperalgesia phenomena, current topical and intradermal capsaicin delivery methods have two key limitations. Intradermal injection can evoke severe chemogenic pain and both delivery methods produce an unstable area of dynamic mechanical allodynia. We present validity studies of a new preparation for capsaicin delivery that overcomes these limitations. The novel capsaicin formulation consists of a water-based semisolid jelly preparation containing 1% capsaicin which is applied topically under adhesive-free occlusion to a small area of the skin. We demonstrate that in healthy human subjects this model evokes areas of flare, punctate hyperalgesia and mechanical allodynia which are equivalent to established models and that these areas are stable over time and reproducible on repeat experiments. The jelly formulation evokes only minimal chemogenic pain and, as the preparation remains in situ throughout the study providing constant capsaicin exposure, a stable area of dynamic mechanical allodynia is produced. These validation studies show that this novel capsaicin administration method is a practical, reliable and viable tool for investigating experimental secondary hyperalgesia.

Administration, Topical↗
PubMed2001

Neurofibromatosis: clinical presentations and anaesthetic implications.

The neurofibromatoses are autosomal dominant diseases that have widespread effects on ectodermal and mesodermal tissue. The commonest member of the group is neurofibromatosis type 1 (NF1) which varies in severity but which can affect all physiological systems. Neurofibromas are the characteristic lesions of the condition and not only occur in the neuraxis but may also be found in the oropharnyx and larynx; these may produce difficulties with laryngoscopy and tracheal intubation. Pulmonary pathology includes pulmonary fibrosis and cystic lung disease. The cardiovascular manifestations of NF1 include hypertension, which may be associated with phaeochromocytoma or renal artery stenosis. Neurofibromas may also affect the gastrointestinal tract and carcinoid tumours may be found in the duodenum. This review documents the aetiology and clinical manifestations of the neurofibromatoses and discusses their relevance to the anaesthetist.

Anesthesia↗
PubMed2001

Subdural haematoma after dural puncture headache treated by epidural blood patch.

Subdural haematoma is a well-documented complication of accidental dural puncture, and is thought to be preventable by prompt treatment with an epidural blood patch. An accidental dural puncture occurred in a 39-yr-old primagravida during the siting of an epidural catheter for pain relief in labour. Twenty hours after the puncture, the mother developed a typical postdural puncture headache, which increased in severity over the subsequent 24 h. An epidural blood patch was performed at 48 h, and this initially relieved the headache. After discharge from hospital, and 14 days after the dural puncture, the headache recurred, together with expressive dysphasia, poor co-ordination and sensory loss in the right arm. A magnetic resonance imaging scan demonstrated a left sided subdural haematoma, which was drained successfully with complete recovery.

Adult↗
PubMed2001

Differences in the neuromuscular capacity and lean muscle tissue in old and older community-dwelling adults.

BACKGROUND: This study investigated whether there was a worsening of the neuromuscular capacity of older adults after the seventh decade of life. METHODS: Fifteen healthy community-dwelling old (< 70 years of age) and 15 older adults (> or = 70 years of age) were assessed for maximal isometric strength (MVC) and force production characteristics, a one-repetition maximum (1-RM) performance, electromyographic (EMG) activity, and bone-free lean tissue (BFLT) mass of the lower extremity. RESULTS: The isometric MVC, 1-RM, and BFLT mass values in the old group were significantly greater than in the older group. In addition, the individual BFLT mass values correlated significantly with the isometric MVC values (r = .85) and the 1-RM scores of the thigh muscle groups (r = .54-.80). The old group generated significantly greater isometric maximal rate of torque development than the older group and performed significantly better at all intervals of the absolute and relative force-time curves. The voluntary muscle activation of the knee extensors of the old group produced significantly higher integrated EMG (iEMG) activity at each epoch in the early iEMG-time curve compared with the old group. CONCLUSIONS: The results suggest that the age-related deterioration in maximal strength measures and rapid force production characteristics in older adults could be related to a reduction in the mass and neural activation of the thigh muscles. The deterioration of the neuromuscular system of community-dwelling older adults may contribute to an increased difficulty in performing daily activities and may increase their risks of tripping and falling.

Aged↗
PubMed2001

Effects of early discharge following breast surgery.

A small group of breast cancer surgery patients were discharged early with axillary drains in situ. The group was examined for wound infection, seroma formation and depression, and compared to a group who stayed in hospital. There was no indication that early discharge increased seroma formation or infection. Anxiety and depression appeared to be less in the early discharge group.

Anxiety↗
PubMed2001

Primary prevention of childhood lead poisoning through community outreach.

BACKGROUND: The prevalence of childhood lead poisoning has substantially decreased in Milwaukee, Wisconsin over the past decade. Nevertheless, by the mid 1990s, 30% of children were still found to have elevated blood levels. OBJECTIVE: To extend the reach of the Milwaukee Health Department (MHD) to previously underserved families in 1 inner city neighborhood with extremely old housing, the Sixteenth Street Community Health Center (SSCHC) implemented, in 1995, the Community Lead Outreach Project (CLOP). Going door-to-door, CLOP attempted to identify children 6 months to 6 years old with elevated blood lead levels (BLL), referring those > or = 20 micrograms/dL to MHD and enrolling those with BLLs 10-19 micrograms/dL in a program of prevention education and environmental clean-up with the specific aim of preventing BLLs increasing to 20 micrograms/dL and above. METHODS: A team of community outreach workers led by a nurse-coordinator visited, over a 4-year period, families in their homes in 13 census tracts surrounding the SSCHC. During the home visits, capillary blood samples for BLLs were drawn, environmental assessments and scoring were conducted, lead poisoning prevention education provided and repair and cleaning of household lead hazards demonstrated. For control and comparison, BLL data for the entire city by ZIP Code and provider were obtained from the Milwaukee Health Department. Odds ratios for changes in the proportions of children screened > or = 10 micrograms/dL were calculated and compared for the years 1996 through 1999. The odds ratios of changes for various populations were compared for significant differences using tests of homogeneity. To control for age confounding, proportions of elevated BBLs for all groups and for all years were age-standardized, using the direct method. RESULTS: Over the entire study, 20.9% of the children screened had BLLs > or = 10 micrograms/dL and 3.0% were > or = 20 micrograms/dL. For 395 children with BLLs 10-19 micrograms/dL enrolled in the CLOP follow-up program, the mean BLL was 12.9 micrograms/dL. Mean levels at the first, second and third follow-up visits were 10.8, 10.3 and 9.8 micrograms/dL respectively, showing an overall decline of 3.1 micrograms/dL or 24%. At the first follow-up visit, 97% of the children tested were < 20 micrograms/dL while 76% were < 10 micrograms/dL. By the second follow-up visit, 100% were < 20 micrograms/dL. Initial environmental scores averaged 24.7, declining to 19.0 at first, 17.8 at second and 14.8 at third follow-up visits. For the entire CLOP population, the proportion of children testing > 10 micrograms/dL declined each year from 46.3% in 1996 to 22.5% in 1999. The geographic area in which CLOP operated recorded the highest screening penetration rate in the city: 61%. The odds ratio for CLOP clients to have elevated blood lead levels at the end of the study period, in contrast with the beginning, was 0.34 compared to 0.55 for the entire city and 0.75 for private physicians serving the same general population. Comparison of odds ratios showed the CLOP target population enjoyed a decrease in rate of elevated BLL 1.6 times that of the city-wide average, p-value = 0.016 and more than double that of the patients of area private providers. CONCLUSIONS: We conclude that the Sixteenth Street Community Health Center Childhood Lead Outreach Project has successfully accessed populations of children with high rates of lead poisoning who had escaped more traditional screening venues and effectively intervened to reduce their BLLs to < 10 micrograms/dL. Moreover, CLOP produced impressive and unanticipated primary prevention benefits in the community at large. The demonstrated ability of community outreach workers to access high-risk populations and reduce exposure to lead hazards suggests the potential of this strategy for extension to other geographic areas, to the patients of private physicians and to address other prevalent, urban health problems like asthma, injuries and violence.

Child↗
PubMed2000

Progesterone attenuates persistent inflammatory hyperalgesia in female rats: involvement of spinal NMDA receptor mechanisms.

The relationship between endogenous gonadal steroid levels and persistent or chronic pain is poorly understood. These studies used an inflammation model to examine the role of the gonadal steroid, progesterone, in the development of persistent pain and hyperalgesia in lactating ovary-intact and ovariectomized rats. The results indicate that constant high plasma levels of progesterone attenuate inflammatory hyperalgesia by a mechanism involving inhibition of N-methyl-D-aspartate receptor activation at the spinal cord level. Since the pattern of high progesterone in lactating rats mimics the progesterone component of the luteal phase of the human menstrual cycle, these findings have significance in persistent or chronic pain conditions that are most prevalent in females.

Animals↗
PubMed2000

Cross-linking of LFA-1 induces secretion of macrophage inflammatory protein (MIP)-lalpha and MIP-1beta with consequent directed migration of activated lymphocytes.

Cross-linking of LFA-1 induces an active locomotory phenotype in T cells. In this study we demonstrate that cross-linking of LFA-1 using a monoclonal antibody results in the secretion of MIP-1alpha and MIP-1beta. Similar results were seen with anti-CD44 but not with anti-transferrin receptor or anti-MHC class 1. We examined the ability of activated lymphocytes to migrate onto a substrate consisting of large protein G-Sepharose beads coated with anti-LFA-1 and anti-CD44. In this system a signal is provided by cells at the point of contact with the beads. Cells migrated to cover the bead surface within 24 h. This contact was shown to be inhibited by the introduction of neutralizing antibodies to MIP-1alpha and MIP-1beta. Hence cross-linking of LFA-1 or CD44 induce chemokine secretion which may be of relevance in directional migration of lymphocytes.

Antibodies, Monoclonal↗
PubMed2000

Mitochondrial oxidative phosphorylation is a downstream regulator of nitric oxide effects on chondrocyte matrix synthesis and mineralization.

OBJECTIVE: Increased chondrocyte nitric oxide (NO) and peroxynitrite production appears to modulate decreased matrix synthesis and increased mineralization in osteoarthritis (OA). Because NO inhibits mitochondrial respiration, this study was undertaken to directly assess the potential role of chondrocyte mitochondrial oxidative phosphorylation (OXPHOS) in matrix synthesis and mineralization. METHODS: We studied cultured human articular chondrocytes and immortalized costal chondrocytes (TC28 cells). We also assessed the effects of antimycin A and oligomycin (inhibitors of mitochondrial complexes III and V, respectively) on chondrocyte mitochondrial respiration, ATP synthesis, and inorganic pyrophosphate (PPi) generation, and the mineralizing potential of released matrix vesicles (MV). RESULTS: Articular chondrocytes and TC28 cells respired at comparable rates. Peroxynitrite and NO donors markedly suppressed respiration and ATP generation in chondrocytes. Because NO exerts multiple effects on chondrocytes, we investigated the primary functions of mitochondrial respiration and OXPHOS. To do so, we identified minimally cytotoxic doses of antimycin and oligomycin, which both induced intracellular ATP depletion (by 50-80%), attenuated collagen and proteoglycan synthesis, and blocked transforming growth factor beta from increasing intracellular ATP and elaboration of PPi, a critical inhibitor of hydroxyapatite deposition. Antimycin and oligomycin also abrogated the ability of the ATP-hydrolyzing enzyme plasma cell membrane glycoprotein 1 (PC-1) to increase chondrocyte PPi generation. Finally, MV from cells treated with antimycin or oligomycin contained less PPi and precipitated >50% more 45Ca. CONCLUSION: Chondrocyte mitochondrial reserve, as NO-sensitive mitochondrial respiration-mediated ATP production, appears to support matrix synthesis and PPi elaboration and to regulate MV composition and mineralizing activity. NO-induced depression of chondrocyte respiration could modulate matrix loss and secondary cartilage mineralization in OA.

Adenosine Triphosphate↗
PubMed2000

Regulation of auxin transport by aminopeptidases and endogenous flavonoids.

The 1-N-naphthylphthalamic acid (NPA)-binding protein is a putative negative regulator of polar auxin transport that has been shown to block auxin efflux from both whole plant tissues and microsomal membrane vesicles. We previously showed that NPA is hydrolyzed by plasma-membrane amidohydrolases that co-localize with tyrosine, proline, and tryptophan-specific aminopeptidases (APs) in the cotyledonary node, hypocotyl-root transition zone and root distal elongation zone of Arabidopsis thaliana (L.) Heynh. seedlings. Moreover, amino acyl-beta-naphthylamide (aa-NA) conjugates resembling NPA in structure have NPA-like inhibitory activity on growth, suggesting a possible role of APs in NPA action. Here we report that the same aa-NA conjugates and the AP inhibitor bestatin also block auxin efflux from seedling tissue. Bestatin and, to a lesser extent, some aa-NA conjugates were more effective inhibitors of low-affinity specific [3H]NPA-binding than were the flavonoids quercetin and kaempferol but had no effect on high-affinity binding. Since the APs are inhibited by flavonoids, we compared the localization of endogenous flavonoids and APs in seedling tissue. A correlation between AP and flavonoid localization was found in 5- to 6-d-old seedlings. Evidence that these flavonoids regulate auxin accumulation in vivo was obtained using the flavonoid-deficient mutant, tt4. In whole-seedling [14C]indole-3-acetic acid transport studies, the pattern of auxin distribution in the tt4 mutant was shown to be altered. The defect appeared to be in auxin accumulation, as a considerable amount of auxin escaped from the roots. Treatment of the tt4 mutant with the missing intermediate naringenin restored normal auxin distribution and accumulation by the root. These results implicate APs and endogenous flavonoids in the regulation of auxin efflux.

Aminopeptidases↗
PubMed2000

High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy.

BACKGROUND & AIMS: The multidrug resistance (MDR) gene codes for a drug efflux pump P-glycoprotein 170 (Pgp-170) expressed on the surface of lymphocytes and intestinal epithelial cells. Inflammatory bowel disease (IBD) poorly responsive to medical therapy may relate to MDR expression because glucocorticoids are known Pgp-170 substrates. METHODS: Using flow cytometry, we measured peripheral blood lymphocyte (PBL) MDR in 153 IBD patients and 50 healthy volunteers, and assessed the relationship between PBL, mucosal intraepithelial lymphocyte (IEL), and mucosal epithelial cell (EC) MDR expression in a further 20 IBD patients and 19 controls. RESULTS: Compared with controls, PBL MDR was significantly elevated in patients with Crohn's disease who required bowel resection for failed medical therapy (mean +/- SEM, 26.7 +/- 2.8 vs. 11.9 +/- 1.0; P <0.0001) and patients with ulcerative colitis who required proctocolectomy for failed medical therapy (20.3 +/- 2.5 vs. 11.9 +/- 1.0; P = 0.001). PBL MDR remained stable over time and was not influenced by disease activity or glucocorticoid therapy. Both PBL and mucosal MDR expression appeared independent of disease activity, and there was a significant correlation between PBL MDR expression and both IEL expression (r = 0.92; P < 0.0001) and EC expression (r = 0.54; P < 0.001). CONCLUSIONS: PBL and mucosal MDR expression may play an important role in determining the response of IBD patients to glucocorticoid therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Non-accidental fractures in infants: risk of further abuse.

OBJECTIVES: To look for features of non-accidental fractures in infants aged under I year and assess the risk of subsequent morbidity and mortality. METHODOLOGY: A retrospective analysis of 99 children aged under 1 year who presented to the Mater Children's Hospital, Brisbane, between January 1990 and December 1993, and were found to have a fracture. The 99 infants were divided into non-accidental and accidental groups. Comparison was made between the two groups for age, sex and type of fracture. Deaths, subsequent injuries and child protection notifications until March 1997 were compared between groups. RESULTS: Of the 99 infants with fracture (64 males, 35 female), the skull and femur were the most prevalent sites of fracture. Twenty-six infants had fractures assessed as non-accidental. This group was younger but did not differ significantly in gender or site of fracture. Infants aged under 4 months had a significantly greater risk of their fracture being non-accidental (P = 0.0007). Subsequent substantiated child protection notifications occurred in nine of the non-accidental group and in one of the accidental group (P = 0.000001). There was no significant difference in the rate of subsequent notifications between those infants with abuse who were removed from their carers and those not removed. Subsequent injuries presenting to hospital occurred in 17 of the accidental group and three of the non-accidental group (P = 0.20). There were no deaths. CONCLUSION: Infants aged under 1 year with fractures have a high prevalence of abuse. The risk of abuse as cause for the fracture is greater in those aged under 4 months. Infants with non-accidental fractures have a high risk of further abuse even with intervention.

Accidents↗
PubMed2000

The choice of compressor effects the aerosol parameters and the delivery of tobramycin from a single model nebulizer.

Recent U.S. Phase III trials of the aerosolized delivery of tobramycin to cystic fibrosis (CF) patients demonstrated a significant improvement in pulmonary function and in sputum bacterial density. These trials used the Pari LC Plus nebulizer and DeVilbiss Pulmo-Aide compressor. This compressor is not generally available in Europe, and its power requirements do not match the European power supply. Thus alternate compressors were evaluated, using the LC Plus nebulizer, in preparation for European clinical trials. Aerosol particle size distribution, nebulization time (min), and the respirable dose of tobramycin (mg within 1-5 mu) were obtained for seven compressor models. The respirable quantity delivered by each of the European compressors (240 Volts, 50 Hz) was compared to the LC Plus and PulmoAide compressor (120 Volts, at 60 Hz). The U.S. system delivered 71.4 mg of the 300 mg instilled dose within the respirable range; using the European compressors, between 63.0 and 74.8 mg was delivered. With a 97% confidence that the delivered tobramycin was within 20% of the standard, we conclude that the SystAm 23ST, MedicAid CR50 and CR60, Pari Master and the Pari Boy compressors are equivalent to the U.S. standard; the Hercules and the SystAm 26ST compressors were not statistically equivalent to the standard. Using the LC Plus nebulizer, five European compressors delivered doses of TOBI that are similar to the doses delivered by the DeVilbiss PulmoAide compressors, and thus may be expected to produce clinical results similar to those of the U.S. trials.

Aerosols↗