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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 253 records · Page 14Linked to original sources
PubMed1996

Multiple roles for endothelin in melanocyte development: regulation of progenitor number and stimulation of differentiation.

Melanocytes in the skin are derived from the embryonic neural crest. Recently, mutations in endothelin 3 and the endothelin receptor B genes have been shown to result in gross pigment defects, indicating that this signalling pathway is required for melanocyte development. We have examined the effects of endothelins on melanocyte progenitors in cultures of mouse neural crest. Firstly, they stimulate an increase in progenitor number and act synergistically with another factor, Steel factor, in the survival and proliferation of the progenitors. These findings are consistent with findings from mice with natural mutations in the endothelin receptor B gene, which show an early loss of melanocyte progenitors. Secondly, endothelins induce differentiation of the progenitors into fully mature pigmented melanocytes. This finding is consistent with the expression of endothelins in the skin of mice at the initiation of pigmentation. The melanocytes generated in endothelin-treated cultures also become responsive to alpha melanocyte-stimulating hormone, which then acts to regulate the activity of the pigmentation pathway. These findings indicate two key roles for endothelin in melanocyte development: regulation of expansion of the progenitor pool and differentiation of progenitors into mature melanocytes.

Cell Count↗
PubMed1996

Interobserver reliability of the chest radiograph in community-acquired pneumonia. PORT Investigators.

OBJECTIVE: To evaluate the interobserver reliability of pulmonary radiographic findings in patients with community-acquired pneumonia (CAP). DESIGN: A prospective, multicenter study. SETTING: Physician offices, medical walk-in clinics, emergency departments, and inpatient wards affiliated with three university hospitals, one community hospital, and one staff model health maintenance organization in three geographic areas. METHODS: Copies of the initial chest radiograph of patients suspected of having CAP were independently read by two staff radiologists at the coordinating university hospital. Interobserver reliability for the interpretation for radiographic findings was assessed by calculation of agreement rates and the kappa statistic. PARTICIPANTS: Adults (age > or = 18 years) with symptoms or signs of CAP and a pulmonary radiographic infiltrate documented by a local study site radiologist. RESULTS: Among the 282 patients whose initial pulmonary radiographs were evaluated, there was agreement between the two staff radiologists on the presence of infiltrate in 79.4% and on the absence of an infiltrate in 6.0% (kappa = 0.37; 95% confidence interval [CI] = 0.22 to 0.52). For the 224 patients with an infiltrate identified by both radiologists, there was further agreement that the infiltrate was unilobar in 41.5% and multilobar in 33.9% (kappa = 0.51; 95% CI = 0.28 to 0.62), pleural effusion was present in 10.7% and absent in 73.2% (kappa = 0.46; 95% CI = 0.33 to 0.50), and the infiltrate was alveolar in 96.3% of patients and interstitial in no patients (kappa = -0.01; 95% CI = -0.03 to 0.00). Among the 210 patients with an alveolar infiltrate, both radiologists classified the infiltrate as lobar in 74.6% and bronchopneumonia in 2.4% (kappa = 0.09; 95% CI = -0.04 to 0.22), and agreed on the presence of air bronchograms in 7.6% and their absence in 52.9% (kappa = 0.01; 95% CI = -0.13 to 0.15). CONCLUSION: In patients with CAP, two university radiologists identified the presence of infiltrate, multilobar disease, and pleural effusion with fair to good interobserver reliability. However, interobserver reliability for the pattern of infiltrate and the presence of air bronchograms was poor.

Adolescent↗
PubMed1996

Effects of four years' treatment with biosynthetic human growth hormone (GH) on body composition in GH-deficient hypopituitary adults.

Short-term trials of growth hormone (GH) substitution in hypopituitary adults have shown beneficial effects on body composition. To evaluate the long-term effects on body composition, we followed thirteen GH-deficient adults (GH < 6 mU/l following standard provocative tests) for 4 years of GH replacement. At yearly intervals, serum insulin-like growth factor I (IGF-I), body weight, body mass index (BMI), waist, waist-to-hip circumference ratio (WHR) and resting systolic (SBP) and diastolic blood pressure (DBP) were determined, and body composition was assessed using three independent methods: total body potassium (TBK), bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Compared to baseline, IGF-I levels increased significantly at 1 (p = 0.0001), 2 (p = 0.0004), 3 (p = 0.006) and 4 years (p = 0.002). Body weight and BMI changed minimally at 1, 2 and 3 years and increased significantly only at the fourth year (p = 0.012 and p = 0.0009, respectively) of GH therapy. Waist and WHR decreased significantly at 1, 2 and 4 years (waist: p = 0.0009, p = 0.0004, p = 0.049; WHR: p = 0.0025, p = 0.012, p = 0.047, respectively). Neither resting SBP nor DBP changed significantly. Fat-free mass (FFM) derived from TBK and BIA increased significantly at 1 (p = 0.004; p = 0.004), 2 (p = 0.003; p = 0.05), 3 (p = 0.005; p = 0.04) and 4 years (p = 0.02; p = 0.002). Using DXA, the increase in FFM was significant at 1 (p = 0.007) and 2 years (p = 0.008) but not at 3 and 4 years. Percentage body fat measured by TBK, BIA and DXA decreased significantly at 1 (p = 0.008; p = 0.003; p = 0.03), 2 (p = 0.018; p = 0.06; p = 0.049) and 4 years (p = 0.03; p = 0.002; p = 0.04). A rise in total body water, calculated from BIA, was observed at 1 year (p = 0.004) and was maintained throughout the treatment period. These data demonstrate that 4 years of GH treatment in hypopituitary adults is associated with sustained improvement in body composition.

Absorptiometry, Photon↗
PubMed1996

Cutting healthcare costs through work force reductions. Studies find what works and what doesn't.

Restructuring to cut costs often involves work force reductions. Two recent studies of restructuring in healthcare organizations have found that how an organization reduces its work force is just as important as whether it does. Organizations that implemented across-the-board staff cuts achieved limited cost savings. They also experienced decreased clinical quality, reduced patient satisfaction, and increased staff turnover. However, organizations that reduced their work forces only after a thorough assessment of work processes and job roles achieved greater cost savings, improved clinical quality, higher patient satisfaction, and less staff turnover.

Cost Savings↗
PubMed1996

[Prenatal management of fetuses with alloimmune thrombocytopenia].

Fetal alloimmune thrombocytopenia is caused by maternal immunization against a fetal platelet alloantigen and transplacental transfer of the antibody into the fetal circulation. Since 10-20% of the fetuses or newborns are threatened by intracranial hemorrhages (ICH) early management is required. Intensive prenatal monitoring should be performed if a maternal HPA-1a antibody is known and a previous infant suffered from thrombocytopenia and/or ICH. Fetal blood sampling (FBS) should be started at 20th to 22nd weeks of gestation to assess fetal phenotype and platelet count. Different concepts to elevate the fetal platelet count have been discussed: corticosteroids, maternal intravenous immunoglobulins (ivIgG), fetal ivIgG and repeated fetal platelet transfusions. In a European survey with data from five centres maternal corticoid treatment and ivIgG infusion were accompanied by increasing fetal platelet counts in only 20 and 24% of the cases, respectively. In fetuses with very low platelet counts only transfusions of compatible platelets in short intervals are able to sustain a safe platelet count. Fetuses with mild thrombocytopenia should be monitored by subsequent FBS since it could be shown that platelet counts tend to decline during gestation. To avoid bleeding complications during and after FBS which was observed in about 5% of the cases every cord vessel puncture should be covered by a platelet transfusion. As no safe and non-invasive therapy exists for fetal alloimmune thrombocytopenia the value of prenatal screening programs in unaffected pregnancies is questionable.

Adrenal Cortex Hormones↗
PubMed1996

Leukemia inhibitory factor and ciliary neurotrophic factor in sensory neuron development.

Leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), and related proteins are potentially involved in several aspects of sensory neuron development. There is evidence that LIF promotes the differentiation of sensory neurons from progenitor cells of neural crest origin. Later in development, LIF, CNTF, oncostatin M and interleukin-6 promote the survival of cultured neurons. Some neurons, like those of the nodose ganglion, respond early in their development to these factors, whereas other neurons, like those of the trigeminal ganglion, respond much later. In addition to promoting sensory neuron survival, there is some evidence that LIF is able to influence neurotransmitter and neuropeptide expression in these neurons. These observations suggest that several kinds of sensory neurons may be influenced in various ways by LIF and related factors at different stages of their development.

Animals↗
PubMed1995

Lineage specification of neuronal precursors in the mouse spinal cord.

We have investigated the differentiation potential of precursor cells within the developing spinal cord of mice and have shown that spinal cord cells from embryonic day 10 specifically give rise to neurons when plated onto an astrocytic monolayer, Ast-1. These neurons had the morphology of motor neurons and > 83% expressed the motor neuron markers choline acetyltransferase, peripherin, calcitonin gene-related peptide, and L-14. By comparison, < 10% of the neurons arising on monolayers of other neural cell lines or 3T3 fibroblasts had motor neuron characteristics. Cells derived from dorsal, intermediate, and ventral regions of the spinal cord all behaved similarly and gave rise to motor neuron-like cells when plated onto Ast-1. By using cells that expressed the lacZ reporter gene, it was shown that > 93% of cells present on the Ast-1 monolayers were motor neuron-like. Time-lapse analysis revealed that the precursors on the Ast-1 monolayers gave rise to neurons either directly or following a single cell division. Together, these results indicate that precursors in the murine spinal cord can be induced to differentiate into the motor neuron phenotype by factors produced by Ast-1 cells, suggesting that a similar factor(s) produced by cells akin to Ast-1 may regulate motor neuron differentiation in vivo.

Animals↗
PubMed1995

Comparative efficacy of oral doses of clindamycin and erythromycin in the prevention of bacteraemia.

Two antibiotics, clindamycin and erythromycin, were compared in a double-blind trial to test their efficacy in the prevention of post-dental extraction bacteraemia with streptococci in a group of 40 healthy patients. Tolerance to the oral doses was tested by questionnaire. Levels of drug in the serum were estimated using a microbiological assay. An in-vitro blood culture system was used as an analogy of the persistence of a bacteraemia in the presence of high levels of antibiotic. Isolates of streptococci were identified to species level. Minimum inhibitory concentrations of clindamycin and of erythromycin for each isolate were estimated. Results showed satisfactory levels of antibiotics in the blood for activity against oral streptococci. Clindamycin was slightly more effective than erythromycin in the prevention of post-extraction streptococcal bacteraemia but that efficacy was only 45%. Clindamycin as a single oral dose of 600 mg was well tolerated by patients compared with erythromycin 1.5 g.

Abdominal Pain↗
PubMed1995

Prophylactic aspirin and risk of peptic ulcer bleeding.

OBJECTIVE: To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less. DESIGN: A case-control study with hospital and community controls. SETTING: Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth. SUBJECTS: 1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls. RESULTS: 144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently. CONCLUSION: No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Steel factor directs melanocyte development in vitro through selective regulation of the number of c-kit+ progenitors.

Studies of mice containing mutations in the genes for a receptor tyrosine kinase, c-kit, or its cognate ligand, Steel factor (SLF), establish that this signaling pathway is required for the development of melanocytes from their precursors in the embryonic neural crest (NC). In order to define the mechanism of this requirement, we have labeled cells expressing c-kit with an anti-c-kit antibody (ACK2) and studied the action of SLF on these cells in cultures of murine trunk NC. c-kit positive (c-kit+) cells first appeared after 2 days in culture and were morphologically indistinguishable from other NC cells. These cells subsequently expressed tyrosinase-related protein, an early marker for the melanocyte lineage, and became pigmented in the presence of a phorbol ester. Further, elimination of the c-kit+ population, by incubating the cultures in ACK2, resulted in the ablation of the melanocyte population, but had no effect on the generation of other neural crest derivatives. These data indicate that c-kit+ cells arising from the neural crest are melanocyte progenitors. The addition of SLF to these cultures stimulated an increase in the number of c-kit+ cells, and further studies indicated that SLF acts as both a survival and a proliferative factor for c-kit+ cells. These findings provide a mechanism of regulation of melanocyte development, whereby c-kit is exclusively expressed by melanocyte progenitors within the neural crest precursor population, and subsequent survival and proliferation of these progenitors is regulated by SLF.

Animals↗
PubMed1995

Cyclin A: function and expression during cell proliferation.

Cyclin A is a key regulatory protein which, in mammalian cells, is involved in both S phase and the G2/M transition of the cell cycle through its association with distinct cdks. Several lines of evidence have also implicated cyclin A in carcinogenesis. Our review concentrates on the role of cyclin A in S phase, in the S/G2 transition and in human carcinogenesis; it will also discuss the transcriptional regulation of cyclin A gene.

Cell Division↗
PubMed1995

Lightwand intubation: II--Clinical trial of a new lightwand for tracheal intubation in patients with difficult airways.

Lightwands have been used to assist in the tracheal intubation of patients with difficult airways for many years. A new lightwand (Trachlight) with a brighter light source and a flexible stylet permits both oral and nasal intubation under ambient light. This study reports the effectiveness of the Trachlight in tracheal intubation in patients with difficult airways. Two groups of patients were studied: Group 1--patients with a documented history of difficult intubation or anticipated difficult airways; Group 2--anaesthetized patients with an unanticipated failed laryngoscopic intubation. In Group 1, the tracheas were intubated using the Trachlight with patients either awake or under general anaesthesia. In Group 2, tracheas were intubated under general anaesthesia using the Trachlight. The time-to-intubation, number of attempts, failures, and complications during intubation for all patients were recorded. Two hundred and sixty-five patients were studied with 206 patients in Group 1, and 59 in Group 2. In most patients, the tracheas were intubated orally (183 versus 23 nasal) during general anaesthesia (202 versus 4 awake) in Group 1. Intubation was successful in all but two of the patients with a mean (+/- SD) time-to-intubation of 25.7 +/- 20.1 sec (range 4 to 120 sec). The tracheas of these two patients were intubated successfully using a fibreoptic bronchoscope. Orotracheal intubation was successful in all patients in Group 2 using the Trachlight with a mean (+/- SD) time-to-intubation of 19.7 +/- 13.5 sec. Apart from minor mucosal bleeding (mostly from nasal intubation), no serious complications were observed in any of the study patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Somatoform and personality disorders: syndromal comorbidity and overlapping developmental pathways.

We review the literature on the relationship between somatoform disorders and personality disorders, which reveals that approximately two in three patients with a somatoform disorder meet criteria for a personality disorder. We suggest that the most clinically salient problems presented by patients with somatoform disorders reflect dysfunctions of personality. We also examine research on the childhood antecedents of somatoform disorders and argue for reconsidering somatoform disorders, along with personality disorders, as disorders of development. Our argument involves rejecting the traditional approach to classification in favour of a prototypical polythetic view. We also suggest that the perspectives of developmental psychopathology and life-span research offer more to this field than the search for biological substrates or principles based on descriptive psychopathology, which to date have yielded meagre research findings with limited clinical utility.

Adolescent↗