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Biomedical subjects

N M Clarke

Publications and source records attributed to N M Clarke.

At least 19 recordsLinked to original sources
PubMed2006

Structure of 12Be: intruder d-wave strength at N=8.

The breaking of the N=8 shell-model magic number in the 12Be ground state has been determined to include significant occupancy of the intruder d-wave orbital. This is in marked contrast with all other N=8 isotones, both more and less exotic than 12Be. The occupancies of the [FORMULA: SEE TEXT]orbital and the [FORMULA: SEE TEXT], intruder orbital were deduced from a measurement of neutron removal from a high-energy 12Be beam leading to bound and unbound states in 11Be.

Journal Article↗
PubMed2001

Radiative proton capture on (6)He.

Radiative capture of protons is investigated as a probe of clustering in nuclei far from stability. The first such measurement on a halo nucleus is reported here for the reaction 6He(p,gamma) at 40 MeV. Capture into 7Li is observed as the strongest channel. In addition, events have been recorded that may be described by quasifree capture on a halo neutron, the alpha core, and 5He. The possibility of describing such events by capture into the continuum of 7Li is also discussed.

Journal Article↗
PubMed2001

Halo structure of (14)Be.

The two-neutron halo nucleus (14)Be has been investigated in a kinematically complete measurement of the fragments ((12)Be and neutrons) produced in dissociation at 35 MeV/nucleon on C and Pb targets. Two-neutron removal cross sections, neutron angular distributions, and invariant mass spectra were measured, and the contributions from electromagnetic dissociation (EMD) were deduced. Comparison with three-body model calculations suggests that the halo wave function contains a large nu(2s(1/2))(2) admixture. The EMD invariant mass spectrum exhibited enhanced strength near threshold consistent with a nonresonant soft-dipole excitation.

Journal Article↗
PubMed2001

Histological abnormalities of the calcaneum in congenital talipes equinovarus.

Six calcaneal fragments from patients aged 2, 3, 4, and 5 years with relapsed talipes, and two normal feet from a 40-week-old stillborn fetus were studied. All tissue was sectioned in the sagittal or coronal plane and stained using alcian blue and sirius red to distinguish cartilage and bone. Immunocytochemistry was performed to illustrate collagen types I and II. Within the clubfoot calcaneum, there were fewer chondrocytes and a diminished number of cartilage canals. Although a growth plate was present, the zones of differentiated chondrocytes were not apparent and the chondrocytes were smaller and flatter. The alcian blue staining within the spherical physis was paler than normal, suggesting that the amount of extracellular proteoglycans was reduced. Overall, the growth plate region of the talipes calcaneum resembled that of a permanent cartilage, like articular cartilage. Abnormalities were also seen in the ossification center. Cartilage spicules were rare, and developing bone frequently abutted directly onto the growth plate cartilage. The relative absence of a primary spongiosa suggested that the physis was virtually inactive and endochondral bone formation was retarded. These findings are consistent with the hypothesis that an intrinsic primary growth disorder causes the formation of a small hypoplastic bone and, subsequently, a smaller foot.

Calcaneus↗
PubMed2001

Human osteoprogenitor growth and differentiation on synthetic biodegradable structures after surface modification.

The ability to generate new bone for skeletal use is a major clinical need. Biomimetic scaffolds that interact and promote osteoblast differentiation and osteogenesis offer a promising approach to the generation of skeletal tissue to resolve this major health-care issue. In this study we examine the ability of surface-modified poly(lactic acid) (PLA) films and poly(lactic-co-/glycolic acid) (PLGA) (75:25) porous structures to promote human osteoprogenitor adhesion, spreading, growth, and differentiation. Cell spreading and adhesion were examined using Cell Tracker green fluorescence and confocal microscopy. Osteogenic differentiation was confirmed with alkaline phosphatase activity as well as immunocytochemistry for type I collagen, core binding factor-1 (Cbfa-1), and osteocalcin. Poor cell growth was observed on nonmodified PLA films and PLGA scaffolds. The polymers were then coupled with RGD peptides [using poly(L-lysine), or PLL] and physical adsorption as well as PLA films presenting adsorbed fibronectin (FN). Both modifications enhanced cell attachment and spreading. On PLA-FN and PLA-PLL-GRGDS films, the osteoblast response was dose dependent (20 pmol/L to 0.2 micromol/L FN and 30 nmol/L to 30 micromol/L PLL-GRGDS) and significant at concentrations as low as 2 nmol/L FN and 30 nmol/L PLL-GRGDS. With optimal concentrations of FN or RGD, adhesion and cell spreading were comparable to tissue culture plastic serum controls. In PLGA (75:25) biodegradable porous scaffolds, coated with FN, PLL-GRGDS, or fetal calf serum for 24 h in alpha MEM alone, prior to growth in dexamethasone and ascorbate-2-phosphate for 4-6 weeks, extensive osteoblast impregnation was observed by confocal and fluorescence microscopy. Cell viability in extended culture was maintained as analyzed by expression of Cell Tracker green and negligible ethidium homodimer-1 (a marker of cell necrosis) staining. Alkaline phosphatase activity, type I collagen, Cbfa-1, and osteocalcin expression were observed by immunocytochemistry. Mineralization of collagenous matrix took place after 4 weeks, which confirmed the expression of the mature osteogenic phenotype. These observations demonstrate successful adhesion and growth of human osteoprogenitors on protein- and peptide-coupled polymer films as well as migration, expansion, and differentiation on three-dimensional biodegradable PLGA scaffolds. The use of peptides/proteins and three-dimensional structures that provide positional and environmental information indicate the potential for biomimetic structures coupled with appropriate factors in the development of protocols for de novo bone formation.

Aged↗
PubMed2001

The timing of reduction and stabilisation of the acute, unstable, slipped upper femoral epiphysis.

We reviewed the management of 100 cases of slipped upper femoral epiphysis treated over a period of 26 years. A total of 14 slips was identified as unstable on admission. These underwent reduction and stabilisation within 24 hours of the onset of severe symptoms. Of the 86 stable slips four progressed to avascular necrosis (AVN), which was not seen in the unstable slips. The literature on slipped upper femoral epiphysis suggests that the acute unstable slip is at higher risk of developing AVN. We recommend reduction and stabilisation of unstable slips within 24 hours of the onset of symptoms in order to reduce the risk of AVN.

Acute Disease↗
PubMed2000

Effect of antimicrobial factors in human milk on rhinoviruses and milk-borne cytomegalovirus in vitro.

Various antimicrobial factors present in human milk were tested for in-vitro antiviral activity against three rhinoviruses (two clinical isolates and rhinovirus 2) and an isolate of cytomegalovirus (CMV) from human milk. These factors included the gangliosides GM1, 2 and 3, sialyl-lactose, chondroitin sulphates A, B and C, prostaglandins E2 and F2alpha, monolaurin, vitamin A and the protein lactoferrin. All were tested for their ability to inhibit growth of the viruses in cell culture. Human milk was also tested for antiviral activity against these viruses. Only vitamin A, monolaurin and lactoferrin inhibited the growth of CMV, whereas both prostaglandins enhanced the growth of this virus at least four-fold. CMV infects infants from milk but, nevertheless, the milk-borne CMV isolate showed no special resistance to any of the antiviral factors tested. None of the compounds inhibited or enhanced the growth of the rhinoviruses. However, human milk decreased the growth of some of the rhinoviruses and specific secretory immunoglobulin A (sIgA) neutralised the virus.

Antiviral Agents↗
PubMed2000

Displaced supracondylar fractures of the humerus in children. Audit changes practice.

We performed an audit of 71 children with consecutive displaced, extension-type supracondylar fractures of the humerus over a period of 30 months. The fractures were classified according to the Wilkins modification of the Gartland system. There were 29 type IIA, 22 type IIB and 20 type III. We assessed the effectiveness of guidelines proposed after a previous four-year review of 83 supracondylar fractures. These recommended that: 1) an experienced surgeon should be responsible for the initial management; 2) closed or open reduction of type-IIB and type-III fractures must be supplemented by stabilisation with Kirschner (K-) wires; and 3) K-wires of adequate thickness (1.6 mm) must be used in a crossed configuration. The guidelines were followed in 52 of the 71 cases. When they were observed there were no reoperations and no malunion. In 19 children in whom they had not been observed more than one-third required further operation and six had a varus deformity. Failure to institute treatment according to the guidelines led to an unsatisfactory result in 11 patients. When they were followed the result of treatment was much better. We have devised a protocol for the management of these difficult injuries.

Bone Wires↗
PubMed2000

Physiological cell death of chondrocytes in vivo is not confined to apoptosis. New observations on the mammalian growth plate.

Chondrocytes at the lower zone of the growth plate must be eliminated to facilitate longitudinal growth; this is generally assumed to involve apoptosis. We attempted to provide definitive electron-microscopic evidence of apoptosis in chondrocytes of physes and chondroepiphyses in the rabbit. We were, however, unable to find a single chondrocyte with the ultrastructure of 'classical' apoptosis in vivo, although such a cell was found in vitro. Instead, condensed chondrocytes had a convoluted nucleus with patchy chromatin condensations while the cytoplasm was dark with excessive amounts of endoplasmic reticulum. These cells were termed 'dark chondrocytes'. A detailed study of their ultrastructure combined with localisation methods in situ suggested a different mechanism of programmed cell death. In addition, another type of death was identified among the immature chondrocytes of the chondroepiphysis. These cells had the same nucleus as dark chondrocytes, but the lumen of the endoplasmic reticulum had expanded to fill the entire non-nuclear space, and all cytoplasm and organelles had been reduced to dark, worm-like inclusions. Since these cells appeared to be 'in limbo', they were termed 'paralysed' cells. It is proposed that 'dark chondrocytes' and 'paralysed cells' are examples of physiological cell death which does not involve apoptosis. It is possible that the confinement of chondrocytes within their lacunae, which would prevent phagocytosis of apoptotic bodies, necessitates different mechanisms of elimination.

Acid Phosphatase↗
PubMed2000

Relapse in staged surgery for congenital talipes equinovarus.

Between 1988 and 1995, we studied 91 club feet from a series of 120 recalcitrant feet in 86 patients requiring surgical treatment. There were 48 boys and 20 girls. The mean age at operation was 8.9 months. Surgery consisted of an initial plantar medial release followed two weeks later by a posterolateral release. This strategy was adopted specifically to address the problems of wound healing associated with single-stage surgery and to ascertain the rate of relapse after a two-stage procedure. Immobilisation in plaster was used for three months followed by night splintage. The feet were classified preoperatively and prospectively into four grades according to the system suggested by Dimeglio et al. Grade-1 feet were postural and did not require surgery. All wounds were closed primarily. One superficial wound infection occurred in a grade-4 foot and there were no cases of wound breakdown. The rate of relapse was 20.4% in grade-3 and 65.4% in grade-4 feet. Two-stage surgery for the treatment of club foot seems to be effective in the reduction of wound problems but does not appear to give significantly better results in terms of relapse when performed for more severe deformities.

Clubfoot↗
PubMed1999

"Cell paralysis" as an intermediate stage in the programmed cell death of epiphyseal chondrocytes during development.

The efficient elimination of apoptotic cells depends on heterophagocytosis by other cells, which is difficult or impossible when the dying cells are embedded in an extracellular matrix. This situation is exemplified by the epiphyseal chondrocytes during the development of the chondroepiphyses of long bones. A detailed ultrastructural study identified an unusual type of epiphyseal chondrocyte which contained a very dark nucleus with irregular patches of condensed chromatin and a crenated nuclear membrane. The cytosol consisted of excessively expanded endoplasmic reticulum lumen, containing "islands" of cytoplasm and organelles. Since these cells appeared to be "in limbo," neither viable nor dead, they are referred to as "paralyzed" cells. By studying cells of intermediate morphologies, we were able to demonstrate the sequence of events leading to cell paralysis. It is proposed that the paralysis represents an intermediate state in the physiological cell death of epiphyseal chondrocytes in which destruction is orderly and avoids a inflammatory, potentially locally destructive, reaction. The cell is rendered paralyzed in terms of function but impotent in respect of damaging consequences. Paralysis is compared and contrasted with apoptosis, autophagocytosis, and necrosis and may represent another mode of programmed cell death in situations where cells are immature and/or where phagocytosis by neighboring cells is difficult.

Animals↗
PubMed1998

The role of magnetic resonance imaging in the investigation of spinal dysraphism in the child with lower limb abnormality.

A review of magnetic resonance imaging (MRI) performed to exclude the presence of spinal dysraphism in children presenting with lower limb pathology is unrewarding in the absence of abnormal neurology. Over a 5-year period, 29 children ages 2 weeks to 15 years with a mean age of 6 years presenting with lower limb abnormalities were referred for MRI of the spine to exclude an occult neurologic cause for the deformities. More than one limb abnormality, for example pes cavus and limb length discrepancy, was present in 93% of the children, and 11 children had severe or recurrent talipes equinovarus deformity. Only two children (7%), both of whom had abnormal limb neurology, had abnormal MRI scans. In the absence of a demonstrable neurologic deficit in the lower limb, there appears to be no advantage in requesting MRI of the spine in children presenting with lower limb abnormality.

Child↗
PubMed1998

Initiation of the bony epiphysis in long bones: chronology of interactions between the vascular system and the chondrocytes.

Many events occur concurrently during the initiation of the secondary ossification center in the cartilaginous epiphyses of long bones. We have investigated the chronology of interactions between the vascular system and epiphyseal chondrocytes by culturing explanted heads of femurs and humeri from pre- and neonatal rabbits on the chorioallantoic membrane (CAM) of growing chick embryos. We confirmed that, on the whole, the epiphyseal cartilage was resistant to vascular invasion, whereas the physeal growth plate was resorbed. However, new CAM-derived cartilage canals occasionally penetrated through the articular surface. This caused death of those chondrocytes in the immediate vicinity of the canal but no further reaction. If explants already contained a bony epiphysis and were halved prior to culture, CAM-derived vessels were attracted to the spongiosa. From there they pushed into the uncalcified cartilage, indicating that calcification was not a prerequisite for vascular invasion. Where at least two vessels were in apposition, a new pseudo-ossification center was initiated: chondrocytes became hypertrophic and the matrix calcified. This suggests that cumulative release of diffusible factors from more than one vessel was the trigger for chondrocyte hypertrophy, which, in turn, led to the initiation of the bony epiphysis. CAM cultures thus provide an experimental model for both the quiescent angiogenesis of cartilage canal formation and the reactionary angiogenesis associated with chondrocyte hypertrophy. By exploiting the different anatomy of CAM-derived vascularity, events that occur concurrently in vivo can be specially separated in CAM culture.

Allantoin↗
PubMed1998

Factors regulating the rat insulin-like growth factor-binding protein-1 response to octreotide.

Insulin-like growth factor-binding protein-1 (IGFBP-1) production is increased by somatostatin and its analogues. In order to determine the time course and identify possible mechanisms of this increase in vivo we administered octreotide to rats and determined IGFBP-1 concentrations by RIA. After 60 min of anaesthesia, the mean baseline IGFBP-1 concentrations were 166 (95% confidence interval 123 to 225) ng/ml and increased in saline-infused animals to 729 (488 to 1086) ng/ml after 180 min. IGFBP-1 was stimulated transiently in response to octreotide, with circulating IGFBP-1 concentrations peaking at 1605 (1220 to 2111) ng/ml at 105 min during a continuous infusion of octreotide (100 micrograms/kg per h). In conscious chronically cannulated rats, baseline IGFBP-1 concentrations were 22 (18 to 28) ng/ml, 8-fold less than in the anaesthetised state, and were stimulated in the short term after administration of an octreotide bolus (100 micrograms/kg s.c.) to reach 88 (62 to 126) ng/ml at 60 min. A similar response was seen after i.v. administration to conscious rats. Intravenous bolus of octreotide (100 micrograms/kg) in rats anaesthetised for 3 h resulted in an increase in IGFBP-1 to peak at 1556 (1268 to 1910) ng/ml at 60 min. The IGFBP-1 response to octreotide was diminished in high-fat fed hyperinsulinaemic rats. The pattern of disappearance of iodinated IGFBP-1 from the circulation was not influenced by octreotide. The changes in GH, insulin and glucose concentrations alone did not sufficiently account for the patterns of response observed. We conclude that, in rats, octreotide stimulates IGFBP-1 acutely and this response is potentiated by factors related to anaesthesia.

Animals↗
PubMed1998

Regulation of insulin-like growth factor-binding protein-3 ternary complex formation in pregnancy.

The IGFs are believed to be important in pregnancy and are implicated in the pathophysiology of pre-eclampsia. In adults the IGFs circulate primarily with IGF-binding protein-3 (IGFBP-3) and an acid-labile glycoprotein (ALS) in a 140 kDa complex which limits IGF bioavailability. Less than 10% of IGFBP-3 is in lower molecular weight forms. We have investigated the developmental regulation of the IGF/IGFBP system in normal and pre-eclamptic pregnancies with particular emphasis on the IGFBP-3 ternary complex. Circulating levels of IGF-I, IGFBP-3 and ALS, and their degree of association in the ternary complex in the fetus increased with gestational age. In neonatal serum from deliveries <35 weeks' gestation IGFBP-3 was predominantly in 30-50 kDa form(s) and ALS was a limiting factor for ternary complex formation. In serum from deliveries >35 weeks both ALS and IGFs were limiting but approximately 25% of IGFBP-3 was unable to form the ternary complex even in the presence of excess ALS and IGF-I. Serum IGFBP-1, -2 and -6 concentrations tended to decrease with increasing gestational age. In pre-eclamptic pregnancies, amniotic fluid IGFBP-2, -3 and -6 levels decreased with gestational age while IGFBP-1 levels did not show the normal decline. We speculate that the endocrine IGF system develops in the fetus during the third trimester of pregnancy when ALS levels increase.

Adult↗
PubMed1997

Monitoring the treatment of developmental dysplasia of the hip with the Pavlik harness. The role of ultrasound.

We report the six-year results of a prospective, controlled demographic trial of developmental dysplasia of the hip (DDH) treated in the Pavlik harness using ultrasound supervision. Our aim was to assess the value of ultrasound and its role in monitoring reduction in the harness, in terms of progression or failure of reduction at an early state. From 1988 to 1994, a total of 221 patients with 370 ultrasonographically abnormal hips was treated in the Pavlik harness. This represents a treatment rate for the Southampton district of 5.1 per 1000 live births. Sixteen hips in 12 patients were not reduced in the harness and required surgical treatment; 95.7% were successfully reduced. One case of mild avascular necrosis (0.3%) was identified in those treated by harness alone. Of the 221 patients 87.8% remain under radiological review, with 3.2% of affected hips showing continued, mild acetabular dysplasia. We conclude that ultrasound monitoring has led to an acceptably low level of intervention, a high reduction rate and minimal iatrogenic complications. The trial is continuing.

Algorithms↗
PubMed1997

Improving the outcome of paediatric orthopaedic trauma: an audit of inpatient management in Southampton.

The patterns, management and outcome of non-fatal orthopaedic injury in childhood was audited over a 1 year period in Southampton. A computer-based audit (1 September 1993 to 31 August 1994) was conducted of all children aged under 15 years who were admitted to the orthopaedic unit after accidental injury. Management was audited by studying the primary conservative and operative treatment methods employed. Treatment outcome was evaluated in terms of need for secondary operative treatment, salvage internal fixation, length of hospital stay and unplanned readmission. In all, 398 children, representing 50/10,000 of the local paediatric population, were admitted with a traumatic injury. There was a significant (P < 0.001, Kolmogorov-Smirnov) seasonal variation in admission rate. There were 87.3% admissions required for fractures, 8.5% after soft tissue injury and 2.2% after joint injury. The following areas were identified where management and outcome could be improved: 1 A 12.1% readmission rate (47/346) in children with fractures owing to a 16% incidence of loss of position after closed reduction of distal radial, forearm shaft and distal humeral fractures. 2 In all, 24% of internal fixation procedures were performed as 'salvage' after failure of conservative treatment, entailing either reoperation during the initial admission or a further unplanned readmission. 3 A prolonged inpatient stay for patients with femoral fractures owing to a wide variation in treatment method. The outcome of non-fatal orthopaedic injury can be improved through the selective use of primary internal fixation of distal radial and humeral fractures and the close adherence to a management algorithm in femoral fractures. There may be a role for more specialised supervision of primary treatment of these particular fractures.

Adolescent↗