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Biomedical subjects

R M Smith

Publications and source records attributed to R M Smith.

At least 19 recordsLinked to original sources
PubMed2007

Degenerative meniscus tears and mobility impairment in women with knee osteoarthritis.

OBJECTIVE: Meniscus tears are often presumed to be associated with a traumatic event, but they can also occur as a result of the cartilage degeneration process in osteoarthritis (OA). The aim of this paper is to describe the prevalence and clinical correlates of degenerative meniscus tears in women with knee OA. METHOD: The subjects were women screened for a double-blind, sham-exercise controlled clinical trial for women over 40 years of age with OA in at least one knee, according to American College of Rheumatology (ACR) clinical criteria. The presence of meniscus tears was assessed via a 3T Intera (Philips Medical Systems) magnetic resonance image (MRI). Clinical examination included a history of arthritis onset and physical examination of the lower extremities. Physical assessments included body composition, muscle strength, walking endurance, gait velocity, and balance. In addition, pain and disability secondary to OA, physical self-efficacy, depressive symptoms, habitual physical activity level and quality of life were assessed via questionnaires. RESULTS: Almost three-quarters (73%) of the 41 subjects had a medial, lateral, or bilateral meniscus tear by MRI. Walking endurance and balance performance were significantly impaired in subjects with a degenerative meniscus tear, compared to subjects without tears, despite similar OA duration, symptoms, and disability, body composition, and other clinical characteristics. CONCLUSION: Meniscus tears, diagnosed by MRI, are very common in older women with knee OA, particularly in the medial compartment. These incidentally discovered tears are associated with clinically relevant impairments of balance and walking endurance relative to subjects without meniscus tears. The explanation for this association requires further study.

Aged↗
PubMed2006

Impact of diabetes on haemoglobin levels in renal disease.

AIMS/HYPOTHESIS: Anaemia is a common complication of renal impairment. It has been suggested that renal failure secondary to diabetes is associated with more severe anaemia, but this has not been clearly substantiated in the published literature. To clarify this, we undertook a single centre, retrospective study to identify the impact of diabetes on anaemia associated with renal impairment. MATERIALS AND METHODS: Information on clinical, biochemical and haematological parameters of 2,052 stable ambulatory patients attending a single tertiary referral renal unit was collected. The impact of diabetic kidney disease on haemoglobin levels at all degrees of renal impairment was studied by comparison with patients with non-diabetic kidney disease after correcting for other commonly associated variables that influence anaemia in patients with renal impairment. RESULTS: Linear regression analysis showed lower haemoglobin in patients with diabetic kidney disease (p < 0.01). At chronic kidney disease (CKD) stages 3, 4 and 5, mean haemoglobin levels in patients with diabetic kidney disease compared with those in patients with non-diabetic kidney disease were 129.5 vs 136.9 g/l (p < 0.001), 120.5 vs 126.9 g/l (p < 0.001) and 107.1 vs 115.9 g/l (p < 0.01), respectively. At CKD stage 4 and 5 the two groups were comparable for ferritin, plasma intact parathyroid hormone levels, ACE inhibitor use and length of follow-up by a nephrologist. CONCLUSIONS/INTERPRETATION: Diabetic kidney disease is associated with lower haemoglobin in comparison with non-diabetic kidney disease, especially at GFR <60 ml/min.

Anemia↗
PubMed2006

Health-related behaviours as predictors of mortality and morbidity in Australian Aborigines.

OBJECTIVE: To examine predictors of coronary heart disease (CHD) and all-cause mortality in Aboriginal Australians. METHOD: In 1988-89, a survey of Western Australian Aborigines (256 women, 258 men) aged 15-88 years documented diet, alcohol and smoking habits. Linkage to mortality and hospital admissions to the end of 2002 provided longitudinal data for modelling of coronary heart disease endpoints and all-cause mortality using Cox regression. RESULTS: Coronary heart disease risk increased with smoking (HR 2.62, 95% CI: 1.19, 5.75), consumption of processed meats >once/week (HR 2.21, 95% CI: 1.05, 4.63), eggs >twice/week (HR 2.59, 95% CI: 1.11, 6.04) and using spreads on bread (HR 3.14. 95% CI: 1.03, 9.61). All-cause mortality risk was lower with exercise >once/week (HR 0.51, 95% CI 0.26, 1.05), increased in ex-drinkers (HR 3.66, 95% CI: 1.08, 12.47), heavy drinkers (HR 5.26, 95% CI: 1.46, 7.52) and with consumption of take away foods >nine times/month (HR 1.78, 95% CI 0.96, 3.29). Greater alcohol intake, smoking and adverse dietary choices clustered in 53% of men and 56% of women and increased risk of coronary heart disease (HR 2.1, 95% CI: 1.1, 4.0) and all-cause mortality (HR 2.3, 95% CI: 1.2, 4.2). CONCLUSION: Lifestyle in Aboriginal Australians predicts coronary heart disease and all-cause mortality. Clustering of adverse behaviours is common and increases risk of coronary heart disease and death.

Adolescent↗
PubMed2005

Radiation exposure to the hands of orthopaedic surgeons: are we underestimating the risk?

INTRODUCTION: Previous studies reported that the radiation exposure to the hands of orthopaedic surgeons was far below the acceptable limit. However, the risk could have been underestimated as some factors were overlooked, namely monitoring trainees during average workload, placing dosimeters over the most susceptible locations, measuring the cumulative dosage of radiation and considering the dose limit for non-classified workers. MATERIALS AND METHODS: We performed a prospective study in two centres to estimate the radiation dose to the hands of two consultant trauma surgeons and two trainees (one assisting and one operating) while performing 47 fluoroscopy-assisted procedures. We used validated thermoluminescent dosimeters (TLDs) rings and fingerstalls for monitoring the cumulative dosage. RESULTS: Trainees were at higher risk while performing intramedullary nailing and during assistance. Higher radiation doses were recorded from dominant index fingers and particularly fingertips. CONCLUSION: The risk of radiation exposure appears to be higher than previously reported. Fingertips are more susceptible to radiation exposure and should therefore be monitored in forthcoming studies.

Fluoroscopy↗
PubMed2005

Double-crush syndrome after acetabular fractures. A sign of poor prognosis.

Injury to the sciatic nerve is one of the more serious complications of acetabular fracture and traumatic dislocation of the hip, both in the short and long term. We have reviewed prospectively patients, treated in our unit, for acetabular fractures who had concomitant injury to the sciatic nerve, with the aim of predicting the functional outcome after these injuries. Of 136 patients who underwent stabilisation of acetabular fractures, there were 27 (19.9%) with neurological injury. At initial presentation, 13 patients had a complete foot-drop, ten had weakness of the foot and four had burning pain and altered sensation over the dorsum of the foot. Serial electromyography (EMG) studies were performed and the degree of functional recovery was monitored using the grading system of the Medical Research Council. In nine patients with a foot-drop, there was evidence of a proximal acetabular (sciatic) and a distal knee (neck of fibula) nerve lesion, the double-crush syndrome. At the final follow-up, clinical examination and EMG studies showed full recovery in five of the ten patients with initial muscle weakness, and complete resolution in all four patients with sensory symptoms (burning pain and hyperaesthesia). There was improvement of functional capacity (motor and sensory) in two patients who presented initially with complete foot-drop. In the remaining 11 with foot-drop at presentation, including all nine with the double-crush lesion, there was no improvement in function at a mean follow-up of 4.3 years.

Acetabulum↗
PubMed2005

Over-expression of AMP-activated protein kinase impairs pancreatic {beta}-cell function in vivo.

Treatment of type 1 diabetes by islet transplantation is currently limited by loss of functional beta-cell mass after transplantation. We investigated here whether adenovirus-mediated changes in AMP-activated protein kinase (AMPK) activity, previously shown to affect insulin secretion in vitro, might affect islet graft function in vivo. In isolated mouse and rat islets, insulin secretion stimulated by 17 (vs 3) mmol/l glucose was inhibited by 36.5% (P<0.01) and 43% (P<0.02) respectively after over-expression of constitutively-active AMPK- (AMPK CA) versus null (eGFP-expressing) viruses, and glucose oxidation was decreased by 38% (P<0.05) and 26.6% (P<0.05) respectively. Increases in apoptotic index (terminal deoxynucleotide transferase-mediated deoxyuridine trisphosphate biotin nick end-labelling) (TUNEL)) were also observed in AMPK CA- (22.8 +/- 3.6% TUNEL-positive cells, P<0.001), but not AMPK DN- (2.72 +/- 3.9%, positive cells, P=0.05) infected islets, versus null adenovirus-treated islets (0.68 +/- 0.36% positive cells). Correspondingly, transplantation of islets expressing AMPK CA into streptozotocin-diabetic C57 BL/6 mice improved glycaemic control less effectively than transplantation with either null (P<0.02) or AMPK-DN-infected (P<0.01) islets. We conclude that activation of AMPK inhibits beta-cell function in vivo and may represent a target for therapeutic intervention during islet transplantation.

AMP-Activated Protein Kinases↗
PubMed2004

The GC-MS detection and characterization of reticuline as a marker of opium use.

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.

Alkaloids↗
PubMed2004

The GC-MS detection and characterization of reticuline as a marker of opium use.

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.

Alkaloids↗
PubMed2004

Unusual presentation of sciatica in a 14-year-old girl.

The sciatic nerve can be compressed by a variety of causes, while intervertebral disc herniation is the most common cause of sciatica [Surg. Neurol. 46 (1996) 14], other documented causes include, infection, neoplasm, degenerative disease of a spine, congenital anomalies and traumatic posterior hip dislocation [BMJ 287 (1983) 157]. Sciatic neuropathy in children is uncommon. We present an unusual case of sciatic nerve compression in a 14-year-old-girl that was caused by an avulsion fracture of the ischial tuberosity. The compression was relieved by surgical excision of the avulsed ischial tuberosity.

Adolescent↗
PubMed2004

Distal femoral fractures: long-term outcome following stabilisation with the LISS.

We studied 29 patients with distal femoral fractures stabilised using the less invasive stabilisation system (LISS). Four patients were excluded from the final follow-up (three deaths and one case of quadriplegia). The mean age of the remaining 25 patients (9 males and 16 females) was 60.9 years and the mean follow-up 18 months (range 12-24 months). Eleven patients were tertiary referrals from other hospitals (seven cases were referred due to failure of primary fixation). Overall, there were 12 cases of high-energy trauma (7 open fractures). According to the AO classification, there were 5 Type 33A, 2 Type 33B and 12 Type 33C fractures and 4 Type 32A, 1 Type 32B, 1 Type 32C fractures. Functional assessment was performed using the modified Hospital for Special Surgery (HSS) and the Schatzker and Lambert scores. The average time to union in 22 cases was 3.5 months (range 2-5 months). All of the acute cases united without the need for bone grafting. There were three out of seven cases of non-union in the salvage group still undergoing treatment. The overall result in the acute cases was good and in the salvage cases fair. While this is a small series of patients, our preliminary data indicate favourable results using the LISS in stabilising acute distal femoral fractures. However, when the LISS is used as a revision tool the results seem to be less satisfactory. The system appears to be user-friendly and no technical difficulties were encountered.

Adolescent↗
PubMed2004

Secondary structure and hybridization accessibility of the hepatitis C virus negative strand RNA 5'-terminus.

The positive strand RNA genome of hepatitis C virus (HCV) is transcribed exclusively from a full-length cytoplasmic replication intermediate, the negative strand RNA. Despite this essential role in hepatocellular infection, the negative strand has not yet been subjected to extensive molecular characterization, and in comparison with the HCV genome and proteome, remains relatively unexplored as a target for antiviral therapy. The highly conserved negative strand terminal sequences, complementary to the positive strand 5'- and 3'-untranslated regions, are believed to contribute structural features essential for the initiation of positive strand synthesis and the maintenance of template integrity. We investigated the solution structure of the HCV negative strand 5'-terminal region by endoribonuclease mapping and thermodynamic modelling of RNA secondary structure. The enzymatic probing data are consistent with structural models featuring a large terminal stem loop (SL), which constitutes a mirror image of the complementary 3'-X region SL I structure. Nucleotide positions within the negative strand accessible to hybridization were mapped by RNase H digestion in the presence of combinatorial oligonucleotide libraries. The hybridization data further support the existence of a terminal SL, and reveal target sites within the negative strand 5'-terminus which may be susceptible to antisense-mediated inhibition.

3' Untranslated Regions↗
PubMed2004

The functional outcome of severe, open tibial fractures managed with early fixation and flap coverage.

We studied the outcome and functional status of 33 patients with 34 severe open tibial fractures (Gustilo grade IIIb and IIIc). The treatment regime consisted of radical debridement, immediate bony stabilisation and early soft-tissue cover using a muscle flap (free or rotational). The review included standardised assessments of health-related quality of life (SF-36 and Euroqol) and measurement of the following parameters: gait, the use of walking aids, limb-length discrepancy, knee and ankle joint function, muscle wasting and the cosmetic appearance of the limb. Personal comments and overall patient satisfaction were also recorded. The mean follow-up was 46 months (15 to 80). There were 30 Gustilo grade IIIb fractures and and four grade IIIc fractures. Of the 33 patients, 29 had primary internal fixation and four, external fixation; 11 (34%) later required further surgery to achieve union and two needed bone transport procedures to reconstruct large segmental defects. The mean time to union was 41 weeks (12 to 104). Two patients (6.1%) developed deep infection; both resolved with treatment. The mean SF-36 physical and mental scores were 49 and 62 respectively. The mean state of health score for the Euroqol was 68. Patients with isolated tibial fractures had a better outcome than those with other associated injuries on both scoring systems. Knee stiffness was noted in seven patients (21%) and ankle stiffness in 19 (56%); 12 patients (41%) returned to work. Our results compare favourably with previous outcome measurements published for both limb salvage and amputation. All patients were pleased to have retained their limbs.

Adolescent↗
PubMed2003

Segmental tibial fractures: an assessment of procedures in 27 cases.

Twenty-seven patients (two women) with segmental tibial fractures (19 open) were treated in our institution with a mean age of 38.9 years (range 22-67 years) and a mean Injury Severity Score of 11.5 (9-34). Sixteen fractures were stabilised initially with an interlocking nail, seven with an external fixator, one with a hybrid external fixator, two cases were plated and one was treated in plaster. The mean size of the segment was 11.5 cm (range 4-20 cm). Soft tissue coverage was required in 17 cases. There were three cases of compartment syndrome, six cases of superficial infection and four deep infection cases (two of which required amputation). In four cases, excision of the non-viable segment was necessary. Overall, 13 patients were subjected to a second operative procedure (OP) (four external fixators were replaced with the AO solid tibial nail, two Ilizarov bone transports following excision of the dead bone segment, 2 below knee amputations, 3 exchange reamed nailings, 1 LISS plate application for stability and 1 ring fixator for compression of a fracture). Five patients underwent third procedure (two Ilizarov for bone transport, two exchange nailing, and one bone grafting). The mean time to union of the proximal segment was 38.8 weeks (range 10-78 weeks) and 41.4 weeks (range 12-65 weeks) for the distal segment, respectively. The treatment of segmental tibial fractures poses many problems to the surgeon due to the precarious blood supply of the intermediate segment. The risk of non-union delayed union, infection and additional procedures is high as seen in this series of patients.

Adult↗
PubMed2003

Structure-based design of hepatitis C virus inhibitors.

The limitations of current treatment for chronic hepatitis C virus (HCV) infection have prompted the development of novel therapeutic strategies targeting events specific to viral replication. Over the past decade, advances in the study of HCV molecular biology have led to the identification of cis-acting RNA sequences and viral enzymatic activities which present attractive targets for inhibition. High-resolution, three-dimensional structures of the HCV serine protease, helicase and RNA-dependent RNA polymerase have been determined through X-ray crystallographic studies. More recently, solution structures of these proteins and the HCV internal ribosome entry site have been evaluated by nuclear magnetic resonance spectroscopy and electron microscopy. Mutational analysis and structural characterization of these macromolecules in complex with bound substrates, cofactors and inhibitors has further defined the various electrochemical interactions which mediate protein-protein, protein-RNA and other intermolecular contacts. This review will discuss the available structural data with respect to the rational design of HCV enzyme inhibitors and the development of antisense-based therapeutic strategies, such as RNA interference.

Antiviral Agents↗