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M Moran

Publications and source records attributed to M Moran.

At least 19 recordsLinked to original sources
PubMed2006

Can patients with McArdle's disease run?

Patients with McArdle's disease commonly adopt a sedentary lifestyle. This sedentary behaviour, however, usually worsens the limited exercise capacity of these patients. Although eccentric muscle work can be associated with rhabdomyolysis, supervised eccentric training with gradually increasing loads has important advantages compared with conventional concentric work, particularly for patients with a poor cardiorespiratory system. We report the beneficial effects (particularly, increased VO(2peak) (from 14.6 to 30.8 ml/kg/min) and increased gross muscle efficiency (from 13.8% to 17.2%)) induced by a supervised aerobic training programme of 7 months duration including 3-4 running sessions (< or =60 min/session) per week in a 38-year-old patient. These preliminary data suggest the potential therapeutic value of this type of exercise in these patients.

Adult↗
PubMed2006

Distal femoral fractures treated by hinged total knee replacement in elderly patients.

Although the use of constrained cemented arthroplasty to treat distal femoral fractures in elderly patients has some practical advantages over the use of techniques of fixation, concerns as to a high rate of loosening after implantation of these prostheses has raised doubts about their use. We evaluated the results of hinged total knee replacement in the treatment of 54 fractures in 52 patients with a mean age of 82 years (55 to 98), who were socially dependent and poorly mobile. Within the first year after implantation 22 of the 54 patients had died, six had undergone a further operation and two required a revision of the prosthesis. The subsequent rate of further surgery and revision was low. A constrained knee prosthesis offers a useful alternative treatment to internal fixation in selected elderly patients with these fractures, and has a high probability of surviving as long as the patient into whom it has been implanted.

Aged↗
PubMed2005

The clinical dementia rating sum of box score in mild dementia.

BACKGROUND: Making an early diagnosis of dementia is becoming increasingly important, but is difficult in practice. The Clinical Dementia Rating (CDR) scale is a widely used dementia staging instrument, yielding a global score and a summated score (sum of box score). This study examines the utility of the CDR sum of box score, rather than the CDR global score, in making a diagnosis of early dementia. OBJECTIVE: To determine whether the CDR sum of box score is predictive of an ICD-10 diagnosis of dementia in cases with mild cognitive deficits. METHODS: Clinical data recorded on our Memory Clinic database were examined for all patients seen over a 6-year period. Data were extracted from 276 first visits in which patients had scored 0.5 using the CDR global score. We examined the relationship between CDR sum of box score and consensus diagnosis of dementia using logistic regression. RESULTS: We found that increased CDR sum of box score was significantly associated with a higher probability of being assigned an ICD-10 diagnosis of dementia (p < 0.001). The odds ratio for the coefficient of CDR sum of box was 2.3 (95% CI 1.7-3.1), indicating that the likelihood of being diagnosed as having dementia increased by a factor of 2.3 for every point increase on the CDR sum of box score. CONCLUSION: These findings indicate that the CDR sum of box score provides additional information to the CDR global score in mild cases. The CDR sum of box score is a helpful indicator in making/excluding a diagnosis of dementia in people with mild cognitive deficits.

Alzheimer Disease↗
PubMed2005

Myxoma virus M-T5 protects infected cells from the stress of cell cycle arrest through its interaction with host cell cullin-1.

The myxoma virus (MV) M-T5 gene encodes an ankyrin repeat protein that is important for virus replication in cells from several species. Insight was gained into the molecular mechanisms underlying the role of M-T5 as a host range determinant when the cell cycle regulatory protein cullin-1 (cul-1) was identified as a cellular binding partner of M-T5 and found to colocalize with the protein in both nuclear and cytosolic compartments. Consistent with this interaction, infection with wild-type MV (vMyxlac) or a deletion mutant lacking M-T5 (vMyxT5KO) differentially altered cell cycle progression in a panel of permissive and nonpermissive cells. Cells infected with vMyxlac transitioned rapidly out of the G0/G1 phase and preferentially accumulated at the G2/M checkpoint, whereas infection with vMyxT5KO impeded progression through the cell cycle, resulting in a greater percentage of cells retained at G0/G1. Levels of the cul-1 substrate, p27/Kip-1, were selectively increased in cells infected with vMyxT5KO compared to vMyxlac, concurrent with decreased phosphorylation of p27/Kip-1 at Thr187 and decreased ubiquitination. Compared to cells infected with vMyxlac, cell death was increased in vMyxT5KO-infected cells following treatment with diverse stimuli known to induce cell cycle arrest, including infection itself, serum deprivation, and exposure to proteasome inhibitors or double-stranded RNA. Moreover, infection with vMyxlac, but not vMyxT5KO, was sufficient to overcome the G0/G1 arrest induced by these stimuli. These findings suggest that M-T5 regulates cell cycle progression at the G0/G1 checkpoint, thereby protecting infected cells from diverse innate host antiviral responses normally triggered by G0/G1 cell cycle arrest.

Amino Acid Motifs↗
PubMed2004

New technique for inguinal hernia repair.

We compared a new fascia transversalis based hernioplasty with mesh repair techniques which leave the fascia transversalis intact. We prospectively randomized 180 consecutive patients with inguinal hernia to undergo one of the three hernia repair techniques. Hernias were repaired either by using the new fascia transversalis repair-Coskun's hernia repair (FTR), based on the plication of fascia using continuous sutures and followed by a second layer of interrupted or continuous sutures between inguinal ligament and conjoint tendon to distribute the tension, or one of the two mesh repair techniques: anterior (Lichtenstein) or posterior (preperitoneal) repair. Parameters such as age, sex, hernia cause, operation time, type of anesthesia, surgeon's seniority, complications, hospital stay and follow-up were evaluated. Recurrence rates were determined through clinical examination. Effect of prostatism, co-morbid disease, operation time, complications and Nyhus type of hernia on recurrences were also analysed. Most patients in each group were operated on under general anesthesia (78% vs. 80% vs. 85% for FTR, Lichtenstein, and preperitoneal repair, respectively) and by surgeons in training (average 78%). Patients were followed up for a median of 36 months. FTR had less complications and an acceptable time for operation whereas preperitoneal repairs needed more seniority, longer operation time, and caused more complications. There were only 3 (1.6%) recurrences, none in the FTR group and two the in Lichtenstein group during first postoperative year. There was no recurrence in preperitoneal repair group. All patients with recurrences had an operation time longer than 60 min and were operated on by surgeons in training. Two patients with recurrences had prostatism symptoms and chronic cough. We conclude that the new FTR is as effective as mesh repair (either anterior or posterior) with an acceptable rate of recurrences, fewer complications, and that it can be performed by the surgeons in training.

Adolescent↗
PubMed2003

Evaluation of patient concerns before total knee and hip arthroplasty.

The preoperative concerns of patients undergoing total knee or hip arthroplasty were evaluated in a cross-sectional study of 370 patients. Patients completed a questionnaire on 29 concerns, each rated on a scale of 1 (not concerned) to 4 (very concerned). Short Form 12 and Oxford hip or knee scores were also calculated. The results showed that the greatest concern for patients was cancellation of the surgery. This was followed by failure of the surgery to reduce pain, loss of a limb, and joint infection. Concerns regarding scar problems, nursing care, and preoperative tests were the lowest. Women showed statistically significant greater concerns in 9 areas. Younger patients (age, <65) showed increased concerns in 8 areas. Patients who had previously undergone joint arthroplasty were less concerned than those who had not undergone previous lower limb joint arthroplasty for 6 responses. They showed increased concern in 2 areas, nursing care and hospital food. Those undergoing total hip arthroplasty were more concerned about dislocation, dressing, and returning to work (all, P<.05). This study provides useful information for the preoperative counseling of patients and the production of preoperative literature.

Adult↗
PubMed2003

Expect the best, prepare for the worst: surgeon and patient expectation of the outcome of primary total hip and knee replacement.

A cross-sectional study of 100 surgeons and 370 patients awaiting primary total hip or knee replacement was carried out. Oxford hip or knee score questionnaires were sent to the surgeons and patients. They were asked to predict the level of symptoms expected 6 months following surgery. The Oxford scores derive a value of 12-60, with a greater score indicating worsening symptoms. The mean pre-operative score was 45.12 for the hip patients and 42.96 for the knee patients, and the patients expected this to drop to 23.70 and 25.66, respectively, 6 months' postoperatively. This was a significant difference for both groups. The surgeons expected the patients to have a mean postoperative score of 20.91 for the hip group and 22.19 for the knee group. The surgeons' scores were significantly lower than those from the patients. There was a significant difference between the patients' and surgeons' expectations of the results of total knee and hip replacement surgery. The surgeons expected better results than the patients. We believe that this is the first study that directly compares surgeon and patient expectations of lower limb arthroplasty.

Adult↗
PubMed2002

Rheumatoid arthritis presenting as an invasive soft-tissue tumour.

BACKGROUND: We present two patients with advanced rheumatoid arthritis (RA) who were diagnosed as having malignant soft-tissue tumours on magnetic resonance scanning. They were tertiary referrals to a unit specialising in the management of soft-tissue sarcoma. CONCLUSIONS: Both of these tumours subsequently turned out to be benign complications of RA. In both of these cases, no mention was made on the initial radiological request form of the presence of RA. It is essential to give an adequate past medical history when requesting any radiological investigation.

Arthritis, Rheumatoid↗
PubMed2002

Energy metabolism pathways in rat muscle under conditions of simulated microgravity.

Evidence from rats flown in space suggests that there is a decrease in the ability of the soleus muscle to oxidize long chain fatty acids during space flight. The observation suggests that a shift in the pathways involved in muscle fuel utilization in the absence of load on the muscle has occurred. It is also possible that the reduction is part of a general down-sizing of metabolic capacity since energy needs of inactive muscle are necessarily less. The rodent hind limb suspension model has proved to be a useful ground based model for studying the musculo-skeletal systems changes that occur with space flight. Microarray technology permits the screening of a large number of the enzymes of the relevant pathways thereby permitting a distinction to be made between a shift fuel utilization pattern or a general decrease in metabolic activity. The soleus muscle was isolated from 5 control and 5 hindlimb suspended rats (21 days) and the Affymetrix system for assessing gene expression used to determine the impact of hindlimb unloading on fuel pathways within the muscle of each animal. RESULTS: Suspended rats failed to gain weight at the same rate as the controls (337 +/- 5 g vs 318 +/- 6 g, p < 0.05) and muscle mass from the soleus was reduced (135 +/- 3 mg vs 48 +/- 4 mg, p < 0.05). There was a consistent decrease (p < 0.05) in gene expression of proteins involved in fatty acid oxidation in the suspended group whereas glycolytic activity was increased (p < 0.05). Gene expressions of individual key regulatory enzymes reflected these changes. Carnitine palmitoyltransferase I and II were decreased (p < 0.05) whereas expression of hexokinase, phosphofructokinase and pyruvate kinase were increased (p < 0.05). CONCLUSION: Disuse atrophy is associated with a change in mRNA levels of enzymes involved in fuel metabolism indicative of a shift in substrate utilization away from fat towards glucose.

Journal Article↗
PubMed2001

A molecular framework for two-step T cell signaling: Lck Src homology 3 mutations discriminate distinctly regulated lipid raft reorganization events.

Costimulation by CD28 or lipid-raft-associated CD48 potentiate TCR-induced signals, cytoskeletal reorganization, and IL-2 production. We and others have proposed that costimulators function to construct a raft-based platform(s) especially suited for TCR engagement and sustained and processive signal transduction. Here, we characterize TCR/CD48 and TCR/CD28 costimulation in T cells expressing Lck Src homology 3 (SH3) mutants. We demonstrate that Lck SH3 functions after initiation of TCR-induced tyrosine phosphorylation and concentration of transducers within rafts, to regulate the costimulation-dependent migration of rafts to the TCR contact site. Expression of kinase-active/SH3-impaired Lck mutants disrupts costimulation-dependent raft recruitment, sustained TCR protein tyrosine phosphorylation, and IL-2 production. However, TCR-induced apoptosis, shown only to require "partial" TCR signals, is unaffected by expression of kinase-active/SH3-impaired Lck mutants. Therefore, two distinctly regulated raft reorganization events are required for processive and sustained "complete" TCR signal transduction and T cell activation. Together with recent characterization of CD28 and CD48 costimulatory activities, these findings provide a molecular framework for two signal models of T cell activation.

Animals↗
PubMed2001

Co-stimulation and counter-stimulation: lipid raft clustering controls TCR signaling and functional outcomes.

T cell receptor (TCR) antigen recognition induces the formation of a specialized 'immunological synapse' at the T cell : antigen presenting cell (APC) junction. This junction is generated by the recruitment and exclusion of particular proteins from the contact area and is required for T cell activation. We and others have hypothesized that lipid raft/non-raft partitioning provides a molecular basis for protein sorting which organizes the TCR, co-stimulators, signal transducers and the actin cytoskeleton at the T cell : APC interface. Here we discuss the emerging paradigm that co-stimulators induce the directional transport and clustering of lipid rafts at the T cell : APC interface, thus generating platform(s) specialized for processive and sustained TCR signal transduction and T cell activation. We also discuss recent data implicating the involvement of 'counter-stimulators' and other negative regulators which prevent optimal raft clustering at the TCR contact site and, thus, facilitate T cell inactivation and tolerance induction.

Animals↗
PubMed2001

Presentation and outcome of incarcerated external hernias in adults.

BACKGROUND: Incarcerated external hernias are the second most common cause of small-intestinal obstructions. The purpose of this study was to examine the presentation and management of incarcerated external hernia. METHODS: The records of 385 consecutive patients undergoing emergency surgical operation for incarcerated external hernias in a large volume teaching hospital between August 1996 and October 1999 were analyzed. The patients' ages ranged from 15 to 100 years (mean 55.1). There were more men than women (250 and 135, respectively), and 165 (42.9%) patients were over 60 years of age. Inguinal and umbilical hernias were encountered most frequently, in 291 (75.5%) and 48 (12.5%) patients, respectively. The intestine was resected in 53 patients, 31 of whom were over 60 years of age (58.5%). Two hundred fifty-two (84.9%) patients presented 48 hours or more from the onset of symptoms. Significant concomitant diseases were noted in 52 men and 19 women. RESULTS: The overall complication rate amounted to 19.5%, major complications 15.1%. The most serious postoperative complications were pulmonary and cardiovascular. Adult respiratory distress syndrome developed in 10 patients, and congestive heart failure developed in 14 patients. Postoperative mortality was 2.9%. Nine (81.8%) of the dead patients were older than 60. Nine (81.9%) of the dead patients were admitted to hospital more than 24 hours after incarceration. Mortality was high in patients with serious coexisting diseases whereas morbidity was linked with the duration of symptoms prior to admission. CONCLUSIONS: Older age, severe coexisting diseases, and late hospitalization were the main causes of unfavorable outcomes of the management of incarcerated hernias.

Comorbidity↗
PubMed2001

Emergency hernia repairs in elderly patients.

BACKGROUND: Emergency hernia repairs comprise one of the most common procedures performed in elderly patients and also carry a high risk of mortality and morbidity. The aim of this study was to examine the factors that might have an influence on the outcome of emergency hernia repairs in elderly patients. METHODS: A review was made of 189 (120 male and 69 female) patients aged more than 65 years who underwent emergency hernia repair between December 1996 and January 2001 at the surgical emergency unit of our hospital. The patients' ages ranged from 65 to 100 years (mean 72.1). Concomitant diseases were present in 86 (45.5%) patients. Of 189 incarcerated hernias, there were 145 (76.7%) bowel obstructions and 91(48%) strangulations. Necrotic bowel was resected in 36(19%) patients. RESULTS: While overall mortality was 5%, it was found to be 19.4% after bowel resection. Major complications were observed in 48 (25%) patients. Mortality and morbidity were clearly linked with bowel resection. Coexisting cardiopulmonary diseases, misdiagnosis, American Society of Anesthesiologists class, and late admission were also found to be responsible for unfavorable outcomes. CONCLUSIONS: In elderly patients with external hernias early elective surgery should be preferred, and local anesthesia might be the best in order to avoid the increased risks of emergency hernia repairs.

Aged↗
PubMed2001

Reciprocity.

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Education, Medical, Graduate↗