PubMed Health⌕ Search

Biomedical subjects

John Slavin

Publications and source records attributed to John Slavin.

15 recordsLinked to original sources
PubMed2006

Percutaneous radiofrequency ablation for osteoid osteoma: experience with a new treatment.

OBJECTIVE: To review our experience with percutaneous radiofrequency ablation (RFA) for osteoid osteoma. PARTICIPANTS, DESIGN AND SETTING: Retrospective review of 24 patients with osteoid osteoma treated with percutaneous RFA at St Vincent's Hospital, Melbourne, from August 2000 to February 2005. MAIN OUTCOME MEASURES: Initial response to treatment, return of symptoms, time to recurrence, complications and histopathological correlation. RESULTS: In 23 of 24 patients, there was immediate relief of symptoms. One-third of patients had a return of symptoms. The 24 patients underwent a total of 32 RFA procedures. Of the eight patients who had a recurrence, five had an initial lesion > or = 10 mm in maximum diameter. Twenty-three of the 24 patients were pain-free at the end of the study period. Patients were followed up for a median of 26 months. There were no long-term complications. CONCLUSIONS: Percutaneous RFA is a safe and efficacious treatment for osteoid osteoma with a low morbidity rate. Despite recurrence after treatment, re-treatment is simple and effective.

Adolescent↗
PubMed2006

Osteoprotegerin overexpression by breast cancer cells enhances orthotopic and osseous tumor growth and contrasts with that delivered therapeutically.

Osteoprotegerin (OPG) acts as a decoy receptor for receptor activator of NF-kappaB ligand (RANKL), which is a pivotal molecule required for osteoclast formation. In vitro OPG inhibits osteoclast formation and in vivo (administered as Fc-OPG) it reduces hypercalcemia and the establishment of osteolytic lesions in mouse models of tumor cell growth in bone. Osteolysis can be induced by parathyroid hormone-related protein (PTHrP) produced by breast cancer cells that results in an increased osteoblastic RANKL/OPG ratio. We examined the effect of local tumor production of OPG on the ability of breast cancer cells to establish and grow in bone and mammary fat pad. MCF-7 cells or MCF-7 cells overexpressing PTHrP were transfected with full-length OPG and inoculated into the proximal tibiae of athymic nude mice. Mice injected with cells overexpressing PTHrP and OPG showed enhanced tumor growth, increased osteolysis (2-fold compared with MCF-7 cells overexpressing PTHrP), and altered histology that was reflective of a less differentiated (more aggressive) phenotype compared with MCF-7 cells. In contrast, administration of recombinant Fc-OPG reduced tumor growth and limited osteolysis even in mice inoculated with OPG overexpressing cells. Similarly, OPG overexpression by breast cancer cells enhanced tumor growth following orthotopic inoculation. These results indicate that OPG overexpression by breast cancer cells increases tumor growth in vivo and that there are strikingly different responses between therapeutically administered Fc-OPG and full-length OPG produced by tumor cells.

Animals↗
PubMed2006

Histological evaluation of full thickness skin as an interpositional graft in the rabbit craniomandibular joint.

PURPOSE: The purpose of this study is to determine the histological fate of the full thickness skin graft when placed into the temporomandibular joint using a rabbit model. MATERIALS AND METHODS: Fourteen New Zealand white rabbits were used and divided into 3 groups. Two rabbits were used as controls (Group A) whereby a sham operation was undertaken with an incision made and immediately repaired without breaching the joint space of the left craniomandibular joint (CMJ). In 6 rabbits (Group B), the joint capsule of the left CMJ was surgically breached but the articular disc was preserved and the wound was repaired. The remaining 6 rabbits (Group C) also had the left CMJ surgically exposed with preservation of the articular disc and the interpositional placement of a full thickness skin graft that was taken from the skin of their necks. All grafts were placed above the articular disc and head of condyle in the superior joint space and firmly secured to the surrounding tissues with nonresorbable sutures. The rabbits were sacrificed at 1, 3, and 5 months after surgery and the left CMJs were histologically prepared and examined under light microscopy. RESULTS: The condylar head in the regions where the disc was present appeared to closely resemble that of the control rabbits. However, where the disc was breached by inadvertent surgical trauma (Group B), the underlying condyle showed an irregular outline with increased fibrosis and a marked reduction in mature cartilage. In the subarticular bone there was increased osteoblast and osteoclast activity reflecting high bone activity indicative of a remodeling rather than a degenerative process. The interpositional skin grafts in all experimental animals (Group C) were found adjacent to the condyle on the lateral aspect rather than above the condylar head where it was originally sutured in place. Significant atrophy and reduction in the number and size of the skin appendages such as sweat glands and hair follicles was found within the grafted skin of all experimental animals (Group C) compared with normal skin. All the grafts showed evidence of epidermoid inclusion cysts. CONCLUSIONS: The full thickness skin graft is not a suitable interpositional material for the TMJ because of the high risk of epidermoid cyst formation and the propensity for lateral displacement of the graft even when sutured into the appropriate intra-articular position.

Animals↗
PubMed2006

The effects of unilateral discectomy and condylectomy on the contralateral intact rabbit craniomandibular joint.

PURPOSE: The purpose of this study is to determine the effects of unilateral discectomy and condylectomy on the contralateral intact rabbit craniomandibular joint at the histological level. MATERIALS AND METHODS: Fifteen New Zealand white rabbits were used and divided into 3 groups. Three rabbits were used as controls (group A) whereby a sham operation was undertaken without breaching the joint space of the left craniomandibular joint (CMJ). In 6 rabbits (group B), the articular disc of the left CMJ was excised. The remaining 6 rabbits (group C) underwent surgical resection of the left condylar head at the level of the condylar neck. The resultant surgical defects were left to heal without any grafting and the incisions were closed with resorbable sutures. The rabbits were sacrificed at 4, 12, and 20 weeks after surgery and both the left and right CMJs were histologically prepared and examined under light microscopy. RESULTS: In the 4-week group, unilateral discectomy and condylectomy resulted in remodeling of the unoperated right CMJ with histological evidence of flattening of the condylar head which was more pronounced in the condylectomy group. In the 12-week group, the remodeling process in the unoperated right CMJ was less pronounced with most of the activity concentrated in the medial pole, especially in the condylectomy group. The 20-week group showed no obvious signs of remodeling in the unoperated right CMJs in both the discectomy and condylectomy groups. Evidence of condylar regeneration was seen in all groups in the left CMJ which had undergone condylectomy. No evidence of disc regeneration in the operated left CMJ was seen in any of the discectomy groups. CONCLUSIONS: Unilateral discectomy and condylectomy have an early adverse effect on the structural integrity of the contralateral unoperated CMJ which appears to be short lived. The early remodeling effects on the unoperated right CMJ appear to be reversible as the operated left CMJ heals.

Animals↗
PubMed2005

Tuberculosis masquerading as malignancy: a multimodality approach to the correct diagnosis - a case report.

BACKGROUND: Extrapulmonary tuberculosis is one of the great mimickers of medicine, and often masquerades as malignancy. As a result, patients may be referred to oncologists and surgeons for further evaluation and management, delaying the institution of appropriate anti-tuberculous drug therapy. CASE PRESENTATION: We present the case of a 21 year old man with tuberculous osteomyelitis, who was referred to the Bone and Soft Tissue Sarcoma Service at our institution with a provisional diagnosis of malignancy. Further investigation revealed extensive retroperitoneal abdominal and pelvic lymphadenopathy. The recognition of certain patterns on imaging, and finally the isolation of Mycobacterium tuberculosis from tissue samples obtained under image guidance, enabled the correct diagnosis to be made. CONCLUSION: This case highlights the importance of remaining cognisant of the protean manifestations of extrapulmonary tuberculosis, and illustrates the advantage of a clinically directed multi-modality imaging approach to diagnosis.

Journal Article↗
PubMed2005

Accuracy of computed tomography guided core needle biopsy of musculoskeletal tumours.

BACKGROUND: The accurate diagnosis of musculoskeletal tumours is important for successful treatment. Image guided biopsy is gaining increasing acceptance for obtaining tissue for diagnosis. The aim of the present study is to assess the accuracy of computed tomography (CT)-guided core needle biopsy of musculoskeletal tumours. METHODS: This is a retrospective study on a series of 127 patients with a musculoskeletal tumour. The biopsies were performed over a 4-year period from 1998 to 2001. The accuracy of the CT-guided core needle biopsy was determined by comparing the histology of the biopsy with the final histology of the specimen obtained at open biopsy or surgical resection of the tumour. The effective accuracy was determined by the accuracy of the biopsy to distinguish between a benign and malignant tumour. RESULTS: Computed tomography guided core needle biopsy in the present series has an overall accuracy of 80.3%. The effective accuracy as determined by a malignant versus benign lesion was 89%. There were 86 malignant tumours with a biopsy accuracy of 81.4% and there were 41 benign tumours with a biopsy accuracy of 78%. The positive predictive value (PPV) of a malignant tumour is 98.9% and the PPV of benign tumour 90.2%. The most common site of biopsy was from the femur and thigh, together accounting for 39.4% of the tumours. The most common tumours in this series were liposarcoma (n = 12), osteosarcoma (n = 11) and giant cell tumour (n = 11). There were no reported complications arising from the biopsy. CONCLUSION: Computed tomography guided core needle biopsy is a safe and effective procedure that is important in the diagnosis and management of musculoskeletal tumours. It should be performed in a specialized institution with a multidisciplinary musculoskeletal tumour team.

Adolescent↗
PubMed2004

The role of thallium-201 and pentavalent dimercaptosuccinic acid for staging cartilaginous tumours.

INTRODUCTION: Heterogeneity of cartilage tumours may confound accurate diagnosis and grading resulting in under and over treatment. Improved preoperative assessment of malignancy and grade would be invaluable for developing a rational plan for treatment. We examined correlations between nuclear tracer avidity and malignancy grade in cartilage tumours. METHODS: Between 1996 and 2000, 92 consecutive patients with cartilaginous tumours (50 benign, 42 non-metastatic malignant) underwent nuclear scanning. Thallium-201 (TL-201) and pentavalent dimercaptosuccinic acid (DMSAV) were used as nuclear isotopes. Scanning with these agents was performed on separate days 48 hours apart. Static and SPECT images were obtained at 30 m and 4 h after injection of nuclear tracer. Pathology review was undertaken blinded to the results of the nuclear scans and correlations between histologic results and trace uptake at 4 hours examined. RESULTS: 25 patients with negative DMSAV had benign tumours. 15/17 tumours with positive TL-201 had malignant tumours. 11/13 patients with both positive DMSAV and TL-201 scans had intermediate or high grade tumours and 4 of these developed metastases. We have developed an algorithm for the management of patients with tumours that aims to avoid over treatment of low grade tumours and under treatment of high grade tumours. CONCLUSION: Functional nuclear scanning with TL-201 and DMSAV complements other imaging modalities in the management of cartilaginous tumours.

Journal Article↗
PubMed2004

Altered immune system glycosylation causes colitis in alpha1,2-fucosyltransferase transgenic mice.

BACKGROUND AND AIMS: Altered glycosylation of the mucosal barrier has been proposed as a primary defect in the pathogenesis of IBD. Glycosylation defects however may also have a profound influence on immune function. Mice transgenic for human alpha1,2-fucosyl-transferase (hFUT1) have widespread disturbances in cell surface glycosylation and spontaneously develop colitis. The aims of this study were to characterize colitis in hFUT1 mice and to determine whether glycosylation-induced changes of the mucosal barrier or the immune system were critical for its pathogenesis. METHODS: The pathologic features of hFUT1 transgenic mice were characterized. The mucosal barrier was assessed by lectin binding and permeability studies. T-cells and the thymus were assessed by FACS analysis and histology. To isolate the hFUT1 mucosal barrier from the hFUT1 immune system, bone marrow chimeras were generated. RESULTS: Seventy percent of hFUT1 mice raised in SPF conditions developed histologic evidence of colitis. The mucosal barrier demonstrated altered glycosylation but intestinal permeability was preserved. HFUT1 mice were profoundly lymphopenic, with aberrant T-cell markers and thymic medullary hypoplasia. Reconstitution with wild type bone marrow restored thymic morphology and prevented colitis in hFUT1 mice. CONCLUSION: Altered glycosylation in hFUT1 mice has a profound influence on T-cell development and this defect, rather than a mucosal barrier defect, is crucial for the development of colitis.

Animals↗
PubMed2003

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury.

Impaired lung function in severe acute pancreatitis is the primary cause of morbidity and mortality in this condition. Preprotachykinin-A (PPT-A) gene products substance P and neurokinin (NK)-A have been shown to play important roles in neurogenic inflammation. Substance P acts primarily (but not exclusively) via the NK1 receptor. NKA acts primarily via the NK2 receptor. Earlier work has shown that knockout mice deficient in NK1 receptors are protected against acute pancreatitis and associated lung injury. NK1 receptors, however, bind other peptides in addition to substance P, not all of which are derived from the PPT-A gene. To examine the role of PPT-A gene products in acute pancreatitis, the effect of PPT-A gene deletion on the severity of acute pancreatitis and the associated lung injury was investigated. Deletion of PPT-A almost completely protected against acute pancreatitis-associated lung injury, with a partial protection against local pancreatic damage. These results show that PPT-A gene products are critical proinflammatory mediators in acute pancreatitis and the associated lung injury.

Acute Disease↗
PubMed2002

Expression of the chemokines MCP-1/JE and cytokine-induced neutrophil chemoattractant in early acute pancreatitis.

INTRODUCTION: Inflammatory mediators play a critical role in acute pancreatitis. The precise role played by members of the chemokine family remains unclear. AIMS: To investigate the expression of the CC chemokine monocyte chemotactic protein (MCP)-1/JE and the CXC chemokine cytokine-induced neutrophil chemoattractant (CINC) in early acute pancreatitis. METHODOLOGY: Pancreatitis was induced in rats, either by intraperitoneal injection of cerulein or by infusion of 5% sodium taurocholate into the pancreatic duct. Expression of MCP-1/JE and CINC in pancreas and plasma was determined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), Northern analysis, and quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Following induction of acute pancreatitis, MCP-1/JE and CINC immunoreactivity was seen in acinar cells. Infiltrating neutrophils were strongly immunolabeled with an anti-MCP-1/JE antibody, whereas macrophages reacted strongly with an antibody to CINC. Northern analysis and quantitative real-time RT-PCR demonstrated upregulation of MCP-1/JE and CINC mRNA levels in pancreatic tissue. Plasma MCP-1 levels were significantly increased after 6 hours in the cerulein hyperstimulation model (2,444 +/- 93 microg/mL versus control, 1,853 +/- 262 microg/mL; < 0.05). Plasma CINC levels were significantly increased after 6 hours in the cerulein hyperstimulation model (1,680 +/- 134 microg/mL versus control, 725 +/- 128 microg/mL; < 0.005) and after 3 hours in the bile salt infusion model (6,663 +/- 1,405 microg/mL versus control, 2,339 +/- 800 microg/mL; < 0.05). CONCLUSION: CINC and MCP-1/JE may be early mediators of the inflammatory response in acute pancreatitis.

Acute Disease↗
PubMed2002

MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation.

Inflammatory mediators including chemokines play a critical role in acute pancreatitis. The precise nature of early inflammatory signals within the pancreas remains, however, unclear. We examined the ability of isolated pancreatic acini to synthesize CC chemokine monocyte chemotactic protein-1 (MCP-1) and CXC chemokine cytokine-induced neutrophil chemoattractant (CINC) and the response to the secretagogue cerulein at physiological and supraphysiological concentrations. Isolated rat pancreatic acini maintained in short-term (< or =48 h) primary culture constitutively synthesized MCP-1 and CINC. Cerulein (10(-7) M; supramaximal dose) increased production of MCP-1 but not CINC. Cerulein-induced increase in MCP-1 synthesis was accompanied by increase in nuclear factor (NF)-kappaB activation shown by EMSA. Pretreatment with NF-kappaB inhibitors N-acetylcysteine (NAC) and N-tosylphenyalanine chloromethyl ketone (TPCK) blocked cerulein-induced NF-kappaB activation and abolished cerulein's effect on MCP-1 synthesis. Pretreatment with calcium antagonist BAPTA-AM also blocked cerulein's effect on MCP-1 synthesis. These results indicate that isolated acini synthesize MCP-1 and CINC and support the idea of acinar-derived chemokines as early mediators of inflammatory response in acute pancreatitis. Although cerulein hyperstimulation increased MCP-1 synthesis by a calcium-dependent mechanism involving NF-kappaB activation, CINC synthesis was not affected. This suggests that regulation of CC and CXC chemokines within acinar cells may be quite different.

Acetylcysteine↗
PubMed2002

Severe acute pancreatitis is related to increased early urinary levels of the activation Peptide of pancreatic phospholipase A(2).

BACKGROUND/AIM: In acute pancreatitis, it is believed that generalized activation of pancreatic zymogens leads to autodigestion of the pancreas and if excessive to systemic organ injury. Under physiological circumstances, secretory phospholipase A(2) type I (sPLA(2)-I) is activated by trypsinogen, but the extent of this activation in acute pancreatitis is unclear. The aim of this study was to assess time course and level of activation of sPLA(2)-I and trypsinogen in acute pancreatitis, relative to severity. METHODS: 246 patients were enrolled into a prospective European multicenter study. 137 patients had mild and 35 had severe acute pancreatitis, and there were 74 control patients. Urinary samples were taken on admission and at 6-hour intervals for 48 h, then every 12 h up to 72 h, and finally daily for at least 5 days for measurement of the activation peptide of sPLA(2)-I (pro-phosphatase A(2); PROP) and trypsinogen activation peptide. RESULTS: The median maximum PROP values were significantly elevated 48 h after symptom onset in patients with severe acute pancreatitis [1.52 (95% CI 0.8-2.9) nmol/l] as compared with patients with mild acute pancreatitis [0.72 (0.55-1) nmol/l, p = 0.002] and controls [0.49 (0.22-1.2) nmol/l, p = 0.001], but not before or after this time point. The best cutoff point for urinary PROP to predict overall severity was >1 nmol/l < or =48 h after symptom onset (negative predictive value = 88%), but the PROP levels failed to predict the development of multi-organ dysfunction. CONCLUSIONS: Activation of sPLA(2)-I is associated with the early pathogenesis of acute pancreatitis, but not in the development of distant organ damage. This observation raises questions as to the theory of generalized zymogen activation being a principle mechanism involved in the pathogenesis of distant organ damage in acute pancreatitis.

Acute Disease↗