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Biomedical subjects

P M Hughes

Publications and source records attributed to P M Hughes.

At least 19 recordsLinked to original sources
PubMed2006

Multifocal PVNS in a child--followed over 25 years.

Pigmented villonodular synovitis (PVNS) is a rare disorder of unknown aetiology, characterised by a destructive fibrohistiocytic proliferation with production of villous and nodular protrusions. The disease is commonly monoarticular, and involves the knee in 80% of cases. Occurrence in a child and involvement of multiple joints are extremely unusual. We present a case of multiple joint PVNS in a patient who first presented at the age of five and was subsequently followed up for over twenty-five years. The literature on the subject is briefly reviewed.

Child, Preschool↗
PubMed2006

Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment.

We have previously shown that ischaemic lesions are smaller in monocyte chemoattractant protein-1-deficient (MCP-1(-/-)) mice than in wild-type (wt) controls. In addition to its role as a monocyte chemoattractant, monocyte chemoattractant protein-1 (MCP-1) has been proposed to contribute to lesion progression after focal ischaemia by driving local cytokine synthesis by resident glia. To investigate this hypothesis we injected lipopolysaccharide (LPS) into the brain parenchyma of MCP-1(-/-) mice and compared the resulting inflammatory response and production of proinflammatory cytokines to those in wt mice. Microglial and astrocyte morphological activation was the same in the two strains, but MCP-1(-/-) mice showed significantly lower levels of proinflammatory cytokine synthesis; interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) levels were up to 50% lower than in wt controls after 6 h. This reduced synthesis of proinflammatory cytokines occurred well before leucocyte recruitment to the central nervous system (CNS) is observed in this model of acute inflammation and thus cannot be attributed to lower numbers of recruited monocytes at the site of injury. We propose that MCP-1 contributes to acute CNS inflammation by pleiotropic mechanisms. In addition to being a potent chemoattractant for monocytes, we provide evidence here that MCP-1 can modify the responsiveness of CNS glia to acute inflammatory stimuli prior to leucocyte recruitment, thereby acting as a priming stimulus for cytokine synthesis in cells such as microglia.

Acute Disease↗
PubMed2003

Percutaneous laser photocoagulation of osteoid osteomas under CT guidance.

AIM: The aim was to evaluate laser photocoagulation and the use of the Bonopty needle system in the treatment of osteoid osteoma. MATERIALS AND METHODS: Five patients with osteoid osteomas were treated with computed tomography (CT)-guided, percutaneous laser photocoagulation using the Bonopty biopsy system. RESULTS: Complete pain relief was obtained in four patients. In one patient, pain persisted until the 6 weeks follow-up but resolved within 24 h of repeating the procedure. There were no complications, and patients remained symptom free at follow-up of 4-23 months (mean, 14 months). CONCLUSION: CT-guided laser photocoagulation of osteoid osteoma is a minimally invasive technique that represents a cost-effective alternative to surgical excision. The Bonopty needle system allows successful penetration of the sclerotic bone surrounding the nidus with manual pressure alone.

Adolescent↗
PubMed2003

Focal lesions in the rat central nervous system induced by endothelin-1.

Axon injury following cerebral ischemia has received little scientific attention compared to the abundance of information dealing with the pathophysiology of grey matter ischemia. There are differences in the initial response of grey and white matter to ischemia in vitro. In this study we investigate whether the vasoactive peptide, endothelin-1, can generate a focal ischemic lesion in the white matter and compare the findings with endothelin-1-induced lesions in the grey matter. Using a minimally invasive technique to microinject endothelin-1 into selected brain regions, we observed an acute reduction in local MRI perfusion in the injected hemisphere after 1 hour. Twenty-four hours after microinjection of 10 pmoles of endothelin-1, we observed a loss of neurons in the grey matter. At 72 hours, neutrophils were absent and a macrophage/microglia response and astrocyte gliosis were detected. No breakdown in the blood-brain barrier was detected. After injection of 10 pmoles endothelin-1 into the cortical white matter, we observed prolific amyloid precursor protein-positive immunostaining (indicative of axonal disruption) and an increase in tau-1 immunostaining in oligodendrocytes at 6 hours. Similar to the grey matter lesions, no neutrophils were present, a macrophage/microglia response did not occur until 72 hours and there was no disruption in the blood-brain barrier. Focal injections of endothelin-1 into specific areas of the rat CNS represent a model to investigate therapeutic approaches to white matter ischemia.

Animals↗
PubMed2002

Comparison of matrix metalloproteinase expression during Wallerian degeneration in the central and peripheral nervous systems.

The matrix metalloproteinases (MMPs) are a large family of zinc-dependent enzymes which are able to degrade the protein components of the extracellular matrix. They can be placed into subgroups based on structural similarities and substrate specificity. Aberrant expression of these destructive enzymes has been implicated in the pathogenesis of immune-mediated neuroinflammatory disorders. In this study we investigate the involvement of MMPs, from each subgroup, in Wallerian degeneration in both the central and peripheral nervous systems. Wallerian degeneration describes the process initiated by transection of a nerve fibre and entails the degradation and removal of the axon and myelin from the distal stump. A similar degenerative process occurs as the final shared pathway contributing to most common neuropathies. MMP expression and localisation in the peripheral nervous system are compared with events in the CNS during Wallerian degeneration. Within 3 days after axotomy in the peripheral nervous system, MMP-9, MMP-7 and MMP-12 are elevated. These MMPs are produced by Schwann cells, endothelial cells and macrophages. The temporospatial expression of activated MMP-9 correlates with breakdown of the blood-nerve barrier. In the CNS, 1 week after optic nerve crush, four MMPs are induced and primarily localised to astrocytes, not microglia or oligodendrocytes. In the degenerating optic nerve, examined at later time points (4, 8, 12 and 18 weeks), MMP expression was down-regulated. The absence of MMPs in oligodendrocytes and mononuclear phagocytes during Wallerian degeneration may contribute to the slower removal of myelin debris observed in the CNS. The low level of the inactive pro-form of MMP-9 in the degenerating optic nerve may explain why the blood-brain barrier remains intact, while the blood-nerve barrier is rapidly broken down. We conclude that the difference in the level of expression, activation state and cellular distribution of MMPs may contribute to the different sequence of events observed during Wallerian degeneration in the peripheral compared to the CNS.

Animals↗
PubMed2002

The in vitro and in vivo ultrasonographic appearances of the angio-seal percutaneous closure device.

PURPOSE: To assess the ultrasound appearances of the Angio-Seal device in an animal model and in twenty patients following catheterization of the femoral artery. MATERIALS AND METHODS: Ten patients were scanned within 8 hours of their procedure (early group) and 10 at two to four days (delayed group) using Acuson Aspen and Sequoia scanners. Colour flow images were taken and Doppler spectral analysis was performed proximal proximal to, at and distal to the Angio-Seal device. Early and delayed in vitro images were taken in a water bath in which the Angio-Seal device was deployed across a normal porcine aorta for comparison. RESULT: In the ten early patients colour and Doppler drop out were seen in 100 percent and 90 percent respectively compared with 90 percent and 60 percent in the delayed group. The device was seen in 30 percent and 90 percent in early and delayed groups respectively. In the in vitro study the components of the device were seen and a posterior acustic shadow noted. This shadow was less obvious and the polymer anchor more easily seen in the delayed group. CONCLUSION: The Angio-Seal device produces a consistent artifact when scanned soon after deployment. These appearances could potentially be mistaken for a vascular occlusion by the unwary in the appropriate clinical setting of acute post catheterisation lower limb ischaemia however an awareness of the normal sonographic appearances of this device would make this misinterpretation unlikely.

Absorbable Implants↗
PubMed2001

T-cell- and macrophage-mediated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases.

Recent evidence has highlighted the fact that axon injury is an important component of multiple sclerosis pathology. The issue of whether a CNS antigen-specific immune response is required to produce axon injury remains unresolved. We investigated the extent and time course of axon injury in a rodent model of a delayed-type hypersensitivity (DTH) reaction directed against the mycobacterium bacille Calmette-Guérin (BCG). Using MRI, we determined whether the ongoing axon injury is restricted to the period during which the blood-brain barrier is compromised. DTH lesions were initiated in adult rats by intracerebral injection of heat-killed BCG followed by a peripheral challenge with BCG. Our findings demonstrate that a DTH reaction to a non-CNS antigen within a CNS white matter tract leads to axon injury. Ongoing axon injury persisted throughout the 3-month period studied and was not restricted to the period of blood-brain barrier breakdown, as detected by MRI enhancing lesions. We have previously demonstrated that matrix metalloproteinases (MMPs) are upregulated in multiple sclerosis plaques and DTH lesions. In this study we demonstrated that microinjection of activated MMPs into the cortical white matter results in axon injury. Our results show that axon injury, possibly mediated by MMPs, is immunologically non-specific and may continue behind an intact blood-brain barrier.

Amyloid beta-Protein Precursor↗
PubMed2001

Pre-cervical soft tissues: a cautionary note.

Visualization of pre-cervical soft tissue swelling on a lateral radiograph is an important indicator of possible bony injury in the context of cervical spine trauma. We report a case where apparent swelling was in fact an artefact due to an inappropriately placed endotracheal tube. We recommend review of the position of endotracheal tubes when interpreting pre-cervical soft tissue swelling.

Artifacts↗
PubMed2000

Mannosidosis: an unusual cause of a deforming arthropathy.

We report on a case of a deforming arthropathy in a young man with a lysosomal storage disorder. A 31-year-old man with a known diagnosis of mannosidosis presented with a painful swollen right elbow. Radiographs of his right elbow showed a disorganised joint with multiple fragments resembling the appearances of a neuropathic joint. This case provides further evidence that a deforming arthropathy may occur as part of the spectrum of skeletal abnormalities seen in mannosidosis.

Adult↗
PubMed1999

Stillbirth as risk factor for depression and anxiety in the subsequent pregnancy: cohort study.

OBJECTIVE: To assess women's symptoms of depression and anxiety during pregnancy and the postpartum year in the pregnancy after stillbirth; to assess relevance of time since loss. DESIGN: Cohort study with four assessments: in third trimester and 6 weeks, 6 months, and 12 months after birth. SETTING: Outpatient departments of three district general hospitals; subjects' homes. SUBJECTS: 60 women whose previous pregnancy ended in stillbirth after 18 weeks' gestation; 60 matched controls. MAIN OUTCOME MEASURES: Depression and anxiety measured by Edinburgh postnatal depression scale, Beck depression inventory, and Spielberger state-trait anxiety scale. RESULTS: In the third trimester women whose previous pregnancy had ended in stillbirth were significantly more depressed than control women (10.8 v 8.2; P=0.004) and had greater state anxiety (39.8 v 32. 8, P=0.003) The difference was accounted for by those women who conceived less than 12 months after the stillbirth, who were also more depressed at 1 year. Results in those who conceived 12 months or more after stillbirth were similar to those in their controls at all points and showed lower trait anxiety 1 year post partum. One year after the birth 8% of control women and 19% of subjects scored high for depression (P=0.39), with most of the depression among the more recently bereaved (28% v 11%; P=0.18). In the women who had experienced stillbirth, depression in the third trimester was highly predictive of depression 1 year after subsequent birth (P</=0.0005). CONCLUSION: Vulnerability to depression and anxiety in the next pregnancy and puerperium is related to time since stillbirth, with more recently bereaved women at significantly greater risk than controls. As there are problems for mother and infant associated with high anxiety and depression during and after pregnancy, there may be advantage in waiting 12 months before the next conception.

Anxiety Disorders↗
PubMed1999

The position of the popliteal artery in the arthritic knee.

We studied the position of the popliteal artery in 32 patients with primary osteoarthritis of the knee. A total of 45 knees were studied using a noninvasive technique with color-flow duplex scanning. The distance between the popliteal artery and the posterior tibial cortex was measured in various positions of flexion. The distance separating them was found to be maximal between 60 degrees and 90 degrees. The study was repeated in a smaller series of 17 patients (20 knees) after knee replacement but with less conclusive results. We believe the safest position on which to operate in primary arthroplasty is with the knee in flexion, but the safety margins are not the same in revision surgery.

Arthroplasty, Replacement, Knee↗
PubMed1998

The ultrasound diagnosis of posterior shoulder dislocation associated with Erb's palsy.

A case is presented of an infant with Erb's palsy whose posterior dislocation of the humeral head was identified using high-resolution ultrasound following non-diagnostic plain radiographs. Posterior dislocation is associated with Erb's palsy but the diagnosis can be delayed. We suggest the early use of ultrasound in patients with Erb's palsy, as this technique is a safe, quick and reliable method of excluding posterior dislocation.

Birth Injuries↗
PubMed1998

Calcific tendinitis of the gluteus maximus tendon with abnormalities of cortical bone.

Calcific tendinitis of the gluteus maximus tendon is unusual and only eight cases associated with erosions of cortical bone have been reported. We present three further cases which demonstrate variation in appearances of the amorphous calcification in the tendon and cortical erosions on plain radiographs. Isotope bone scans show focal increased activity and computed tomography (CT) clearly demonstrates erosion of cortical bone and calcification within the tendon insertion of gluteus maximus. Follow-up examinations in two cases demonstrated resolution of the changes. We believe this series demonstrates the radiological features and natural history of a common condition occurring at an unusual site. Its recognition is important in order to avoid unnecessary surgical intervention. Resolution of the calcification and cortical erosions has not been previously described.

Adult↗
PubMed1998

Matrix metalloproteinase expression during experimental autoimmune neuritis.

Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome. We have shown recently that BB-1101, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, prevents development of EAN when given from the day of immunization and, more important clinically, reduces disease severity when given from symptom onset. This suggests the involvement of MMP activity in the pathogenesis of EAN. However, the exact function and expression patterns of MMPs in acute inflammation of the PNS have not been investigated. MMP-like enzymes are also involved in the processing of tumour necrosis factor-alpha (TNF-alpha), which has been implicated previously in the pathology associated with EAN. In the present study we investigated the profile of MMP and TNF-alpha expression and their localization in sciatic nerve tissue during EAN, using a semiquantitative competitive reverse transcriptase-coupled polymerase chain reaction and immunohistochemistry. In the normal rat PNS, four of the 10 MMPs studied were constitutively expressed and four MMPs were differentially regulated during EAN. Expression of TNF-alpha was elevated at peak disease severity and localized to Schwann cells, macrophages and endoneurial blood vessels. Expression levels of 92 kDa gelatinase and stromelysin-1 were significantly increased early in the development of EAN and continued to rise, peaking at day 15 coincident with maximum disease severity. Schwann cells and endothelial cells were the main cellular source of these enzymes. Prominent infiltration of inflammatory cells into the sciatic nerve was concordant with a significant increase in the expression levels of matrilysin and macrophage metalloelastase. Both matrilysin and macrophage metalloelastase were detected in invading macrophages, T lymphocytes and resident Schwann cells. The selective upregulation of specific MMPs during EAN and their varied cellular localization suggests that MMPs play a multifactorial role in the aetiology of EAN. Activity of MMPs could participate in the disruption of the blood-nerve barrier, breakdown of the myelin sheath, the release of TNF-alpha, and facilitate leukocyte invasion into the PNS. These observations highlight MMPs as potential targets for therapeutic intervention in acute peripheral neuropathies, such as Guillain-Barré syndrome.

Animals↗