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Biomedical subjects

S M Hay

Publications and source records attributed to S M Hay.

At least 19 recordsLinked to original sources
PubMed2005

An algorithm to standardise the investigation of the undiagnosed traumatic painful adult hip: results at one year.

INTRODUCTION: A significant number of adults present to accident and emergency departments with a painful hip following a fall. When plain radiography is non-diagnostic, it has been traditionally difficult to decide on further investigations as rapid access MRI is still unavailable in many NHS hospitals and, therefore, alternative methods of reliable investigation are required. PATIENTS & METHODS: An algorithm was designed for the management of these patients without the availability of MRI investigation. Over a 60-week period, 278 patients were admitted of whom 31 were adult patients with trauma-related hip pain with no fracture on plain radiography. RESULTS: We revealed 42% had fractures of the hip or pelvic girdle. None of the hip fractures deteriorated to a worse prognostic grade during the investigation process and no hip fractures were missed. CONCLUSIONS: This approach towards a challenging diagnostic problem has been successful in identifying all hip fractures, and no fracture has deteriorated to a worse prognostic group.

Accidental Falls↗
PubMed2001

The effects of carbon dioxide on exercise-induced asthma: an unlikely explanation for the effects of Buteyko breathing training.

OBJECTIVES: To examine the effect of breathing 3% CO2 on exercise-induced asthma (EIA), as a raised airway CO2 level is suggested to mediate the effects of Buteyko breathing training (BBT). DESIGN: Double-blind crossover study, using a standard laboratory-based exercise challenge, with EIA defined as a fall of 15% or greater in the forced expiratory volume in one second (FEV1) within 30 minutes of completing a standard exercise protocol. SUBJECTS: 10 adults with confirmed EIA. INTERVENTION: Air enriched with 3% CO2 during and for 10 minutes after exercise. OUTCOME MEASURES: Maximum percentage fall in FEV1 after exercise. Area under curve (AUC) of the decrease in FEV1 with time. RESULTS: Mean maximum fall in FEV1 was similar: 19.9% with air, and 26.9% with 3% CO2 (P = 0.12). The mean AUC for the total 30-minute post-exercise period was 355 for air and 520 for 3% CO2 (P = 0.07). After discontinuing the 3% CO2 at 10 minutes after exercise, there was a further and sustained fall in FEV1. Mean AUC for the period 10-30 minutes post-exercise was significantly greater for CO2 than air (275 and 137, respectively [P = 0.02]). Mean minute ventilation was increased when subjects exercised breathing 3% CO2: 77.5 L/min for 3% CO2, compared with 68.7 L/min for air (P = 0.02). CONCLUSION: Breathing 3% CO2 during exercise does not prevent EIA. The shape of the FEV1 response curve after 3% CO2 suggests that a greater degree of EIA (because of increased minute ventilation during exercise) was opposed by a direct relaxant effect of CO2 on the airway. Increased airway CO2 alone is an unlikely mechanism for the reported benefits of BBT; nevertheless, further study of the effects of voluntary hypoventilation in asthma is warranted.

Administration, Inhalation↗
PubMed2001

Secondary prevention of osteoporosis: when should a non-vertebral fracture be a trigger for action?

The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

Accidental Falls↗
PubMed2001

Mountain biking injuries in rural England.

BACKGROUND: Off road mountain biking is now an extremely popular recreation and a potent cause of serious injury. AIM: To establish the morbidity associated with this sport. METHODS: Data were collected prospectively over one year on all patients presenting with an injury caused by either recreational or competitive off road mountain biking. RESULTS: Eighty four patients were identified, 70 males and 14 females, with a mean age of 22.5 years (range 8-71). Most accidents occurred during the summer months, most commonly in August. Each patient had an average of 1.6 injuries (n = 133) and these were divided into 15 categories, ranging from minor soft tissue to potentially life threatening. Operative intervention was indicated for 19 patients (23%) and several required multiple procedures. The commonest injuries were clavicle fractures (13%), shoulder injuries (12%), and distal radial fractures (11%). However, of a more sinister nature, one patient had a C2/3 dislocation requiring urgent stabilisation, one required a chest drain for a haemopneumothorax, and another required an emergency and life saving nephrectomy. CONCLUSION: This sport has recently experienced an explosion in popularity, and, as it carries a significant risk of potentially life threatening injury across all levels of participation, the use of protective equipment to reduce this significant morbidity may be advisable.

Adolescent↗
PubMed2000

Maternal protein deficiency causes hypermethylation of DNA in the livers of rat fetuses.

Maternal protein deficiency during pregnancy is associated with changes in glucose tolerance and hypertension in the offspring of rats. In this study the growth of rat fetuses was examined when the dams were fed diets containing 18% casein, 9% casein or 8% casein supplemented with threonine. The extra threonine was added to reverse the decrease in circulating threonine concentrations that occurs when pregnant rats are fed protein-deficient diets. The fetuses of the group fed the low protein diet supplemented with threonine were significantly smaller than those of the control group and not significantly different from those fed low protein. Homogenates prepared from the livers of dams fed the diet containing 9% casein oxidized threonine at approximately twice the rate of homogenates prepared from dams fed the diet containing 18% casein. We conclude that circulating levels of threonine fall as a consequence of an increase in the activity of the pathway that metabolizes homocysteine produced by the transulfuration of methionine. Serum homocysteine was unaffected in the dams fed low protein diets compared with controls, but was significantly greater in dams fed the low protein diet supplemented with threonine. Elevated levels of homocysteine are associated with changes in the methylation of DNA. The endogenous methylation of DNA was greater than that of controls in the livers of fetuses from dams fed the 9% protein diets and increased further when the diet was supplemented with threonine. Our results suggest that changes in methionine metabolism increase homocysteine production, which leads to changes in DNA methylation in the fetus. An increase in maternal homocysteine may compromise fetal development, leading to the onset of glucose intolerance and hypertension in adult life.

Animals↗
PubMed1999

Upregulation of CHOP-10 (gadd153) expression in the mouse blastocyst as a response to stress.

CHOP-10 (also known as gadd153 or Ddit3) is one of the genes overexpressed by mammalian cells exposed to cytotoxic agents or to nutrient stress. The response of this gene to stress was studied in the mouse blastocyst and in F9 embryonal carcinoma cells. When mouse blastocysts were exposed to the alkylating agent MMS, the metabolic inhibitor sodium arsenite or an inhibitor of protein glycosylation tunicamycin, levels of the CHOP-10 mRNA were increased by two- to threefold relative to the mRNA for beta-actin. There was no increase in gene expression when blastocysts were treated with the inhibitor of nucleotide synthesis PALA. These results show that the response of CHOP-10 is dependent on the type of stress applied to the embryo. When F9 embryonal carcinoma cells were treated with MMS or sodium arsenite, CHOP-10 expression was induced by fourfold within 4 hr of treatment. The induction following tunicamycin treatment was slower requiring at least 24 hr. The response to tunicamycin was greater in cells treated with retinoic acid to induce differentiation. The results suggest that there is a link between the extent of glycoprotein synthesis and the sensitivity of CHOP-10 to tunicamycin. The inhibitor PALA did not change CHOP-10 expression in the presence or absence of retinoic acid. In F9 cells an increase in the expression of CHOP-10 was followed by cell death due to apoptosis. The overexpression of CHOP-10 may be a marker for one of the pathways that lead to apoptosis in the blastocyst. These results suggest that there is more than one control system regulating growth arrest in the blastocyst and the fetal outcome may differ depending on the type of stress encountered in culture.

Actins↗
PubMed1999

Changes in bone mass and bone turnover following distal forearm fracture.

Bone loss occurs close to a fracture and is associated with increased bone turnover. Fracture healing itself results in increased markers of bone turnover. But the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following distal forearm fracture. Twenty women (mean age 63 years) were recruited following fracture of the distal radius and ulna. Bone mineral density (BMD) of the hand and forearm were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the fingers was measured at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), free deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and amplitude-dependent speed of sound (AD-SoS). There was a decrease in BMD at the hand and in AD-SoS of the fingers after forearm fracture (p<0.001). This bone loss was maximal for BMD by 6 weeks at 9% (p<0. 001) and remained decreased at 52 weeks. AD-SoS decreased at 12 weeks by 3% (p<0.01) and recovered completely by 52 weeks. Bone formation markers increased between 2 and 4 weeks by 13-52% (p<0. 001), and were still elevated at 52 weeks. Bone resorption markers increased between 2 and 6 weeks by 18-35% and returned to baseline at 52 weeks (TRAcP remained elevated). We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Bone loss after distal forearm fracture did not recover by 52 weeks and most bone turnover markers did not return to baseline.

Acid Phosphatase↗
PubMed1999

Changes in bone mass and bone turnover following ankle fracture.

Bone loss and increased bone turnover are recognized local changes after a fracture, but the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following ankle fracture. Fourteen subjects (7 postmenopausal women and 7 men, mean age 63 years) were recruited following fracture of the distal tibia and fibula. Bone mineral density (BMD) of the ankle and proximal femur were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the calcaneus at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and QUS. There was a significant decrease in BMD at the ultradistal ankle (p<0.001), the trochanteric region of the hip (p<0.01) and QUS of the heel after ankle fracture. This bone loss was maximal for ultradistal ankle BMD by 6 weeks at 13% (p<0.001) and for the trochanter by 26 weeks at 3% (p<0.01). The ankle BMD returned to baseline at 52 weeks but the trochanter BMD did not. Velocity of sound (VOS) decreased at 6 weeks by 2% (p<0.01) and broadband ultrasound attenuation (BUA) by 15% (p<0.01). VOS recovered completely by 52 weeks, but BUA did not return to baseline. Bone formation markers increased significantly between 1 and 4 weeks by 11-78% (p<0.01), and iBAP returned to baseline at 52 weeks but PINP and Oc remained elevated. Bone resorption markers did not increase and NTx was decreased at 52 weeks. We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Ankle BMD and heel VOS recovered at 52 weeks (trochanteric BMD and heel BUA did not) and the bone turnover markers returned toward baseline.

Absorptiometry, Photon↗
PubMed1999

Femoral neck fracture complicating intramedullary nailing of femoral shaft.

Intramedullary nailing of the femur is now established as a routine treatment for femoral shaft fractures. A recognised complication of this technique is the occasional jamming of the intramedullary reaming device within the femoral canal although surprisingly we could not find any reports in the literature. We describe a case in which the removal of such a reamer resulted in an iatrogenic intracapsular fracture of the femoral neck, a serious complication of this problem not previously described in the English literature. This resulted in an intraoperative decision to change the fixation device to accommodate this.

Adult↗
PubMed1999

Expression of the growth arrest genes (GAS and GADD) changes during organogenesis in the rat fetus.

Mammalian cells mount an active response to nutrient limitation by overexpressing the growth arrest specific (GAS) and the growth arrest and DNA damage (GADD) genes. During embryogenesis in rats, there are quantitative and temporal differences in GAS and GADD gene expression during the development of the placenta, heart and kidney. Genes associated with the inhibition of DNA synthesis (p53 and GAS1) were predominantly expressed during the early stages of development, whereas those genes associated with inhibition of protein synthesis [GADD153 (also known as CHOP-10 or Ddit3) and C/EBP-beta] were more highly expressed during the later stages. The GADD45 gene was expressed throughout development. There were distinct periods of GAS3 and GAS6 gene expression during the development of the placenta, heart and kidneys, which is consistent with the proposed roles of these genes in cell interactions. These results show that there is a change in the expression of genes associated with the negative regulation of growth as the fetus develops.

Analysis of Variance↗
PubMed1999

The effects of maternal protein restriction on the growth of the rat fetus and its amino acid supply.

Maternal protein deficiency causes fetal growth retardation which has been associated with the programming of adult disease. The growth of the rat fetus was examined when the mothers were fed on diets containing 180, 90 and 60 g protein/kg. The numbers of fetuses were similar in animals fed on the 180 and 90 g protein/kg diets but the number was significantly reduced in the animals fed on the 60 g protein/kg diet. The fetuses carried by the mothers fed on the 90 g protein/kg diet were 7.5% heavier than those of mothers fed on 180 g protein/kg diet on day 19 of gestation, but by day 21 the situation was reversed and the fetuses in the protein-deficient mothers were 14% smaller. Analysis of the free amino acids in the maternal serum showed that on day 19 the diets containing 90 and 60 g protein/kg led to threonine concentrations that were reduced to 46 and 20% of those found in animals fed on the control (180 g/kg) diet. The other essential amino acids were unchanged, except for a small decrease in the branched-chain amino acids in animals fed on the 60 g protein/kg diet. Both low-protein diets significantly increased the concentrations of glutamic acid+glutamine and glycine in the maternal serum. On day 21 the maternal serum threonine levels were still reduced by about one third in the group fed on the 90 g protein/kg diet. Dietary protein content had no effect on serum threonine concentrations in nonpregnant animals. Analysis of the total free amino acids in the fetuses on day 19 showed that feeding the mother on a low-protein diet did not change amino acid concentrations apart from a decrease in threonine concentrations to 45 and 26% of the control values at 90 and 60 g protein/ kg respectively. The results suggest that threonine is of particular importance to the protein-deficient mother and her fetuses. Possible mechanisms for the decrease in free threonine in both mother and fetuses and the consequences of the change in amino acid metabolism are discussed.

Amino Acids↗
PubMed1998

Effects of nutrient deprivation and differentiation on the expression of growth-arrest genes (gas and gadd) in F9 embryonal carcinoma cells.

The growth-arrest genes (gas and gadd) are widely expressed during mammalian embryogenesis and may be useful as markers of nutritional stress in the embryo. F9 embryonal carcinoma cells have been used to characterize the effect of serum or amino acid deficiency on growth-arrest gene expression in a differentiating embryonic cell. The differentiation markers, homeobox B2 (HoxB2), collagen type IV and laminin B2, were not induced by growth arrest. Treatment with all-trans retinoic acid (RA) produced a dose-dependent increase in alkaline phosphatase activity, which was unchanged in lysine-deficient medium and reduced in low-serum medium. Low-serum medium also reduced HoxB2 expression. There was a transient 2-6-fold increase in mRNAs for C/EBP-beta, gadd153/CHOP-10 and gas5 genes 24 h after transfer to amino-acid-deficient media. The mRNAs for the gas2 and gas6 genes began to rise slowly by 5-10-fold after a delay of approx. 24 h. The transient increases did not occur in low-serum medium where there was a much smaller and slower increase. Differentiation caused 1-2-fold increases in gas2, gas3 and gas6 mRNA levels. The transient overexpression of gas5, gadd153/CHOP-10 and CCAAT-enhancer-binding protein-beta, and the later expression of gas6 mRNAs in response to amino acid deficiency, were not affected by differentiation. RA treatment increased the expression of gas3 and caused gas2 to be transiently overexpressed in amino-acid-deficient medium. Differentiation in serum-deficient medium did not significantly alter the levels of the growth-arrest gene mRNAs. These results show that in F9 cells the growth-arrest genes are expressed sequentially as a result of nutrient stress.

Amino Acids↗
PubMed1998

Acute transient bilateral trigger fingers.

A 30-year-old man presented with bilateral, simultaneous, transient triggering of the middle digits which developed acutely after prolonged and sustained use of a garden rotavator. He was asymptomatic in the period before presentation and has remained so 7 years since.

Adult↗
PubMed1998

Perthes disease affecting three female first-degree relatives.

Perthes disease has an incidence of 1 in 4,750 live births (1 in 3,000 boys, but only 1 in 11,800 girls). Although there is evidence for a genetic predisposition to Perthes disease, more than two family members are rarely affected. We report the first recorded case of Perthes disease affecting three female first-degree relatives.

Child↗
PubMed1998

Effects of maternal vitamin A status on fetal heart and lung: changes in expression of key developmental genes.

Vitamin A is required during pregnancy for fetal lung development. These experiments monitored fetal lung morphology in normal and vitamin A-deficient rats. The expression of elastin and the growth arrest-specific gene 6 (gas6) in fetal and neonatal hearts and lungs was assessed by Northern blotting. In normal-fed rats, elastin and gas6 were expressed in the fetal lung and heart from day 19 of gestation up to day 2 postnatally. Maternal vitamin A deficiency altered fetal lung development. On day 20, the bronchial passageways were less developed and showed reduced staining for elastic fibers, and in the neonates, the relative air space and the size of the sacculi were reduced. In the fetal lung, the mRNAs for elastin and gas6 were reduced to 56 and 68% of the control values, respectively. In the fetal heart, the mRNA for elastin was reduced to 64% of the control value, whereas gas6 was increased twofold. In the neonate, there was no change in elastin expression in the lung or heart, but gas6 expression in the heart was increased twofold. These results suggest that, in the pregnant rat, vitamin A deficiency may retard fetal lung development or influence the differentiation of critical cell lines. The changes in elastin and gas6 expression may be used to identify the cell types affected.

Animals↗
PubMed1997

Fracture of the tibial diaphysis treated by external fixation and the axial alignment grid: a single surgeon's experience.

The results of tibial fracture fixation for 50 unstable closed and open fractures, using the dynamic axial fixator (DAF) and the limb axial alignment grid have been assessed both clinically and radiologically. Each patient has been carefully followed up in a dedicated clinic and each procedure was conducted or directly supervised by the senior author. All patients achieved union, although 16 per cent required a further procedure such as bone grafting or fibula osteotomy to secure this and a further 6 per cent were revised to intramedullary nails. There was a malunion rate of 16 per cent, but no patients requested further treatment for functional problems. The incidence of pin-site infection was 10.4 per cent, each patient taking responsibility for their own pin-site care. There were no deep infections. The results achieved in this series compare favourably with those of other treatment modalities for this fracture, which may often be difficult to manage. Given the stringent adherence to the important principles of fixator application and well supervised follow-up which are practised on this unit, we believe that the results as presented here may well represent the limit achievable with this device. Furthermore, the authors would recommend that the technique remains an important option in tibial fracture management, particularly for the unstable closed and open fractures.

Adolescent↗