Biomedical subjects

Sarah F Smith

Publications and source records attributed to Sarah F Smith.

11 recordsLinked to original sources

PubMed2006

The presence of necrosis and/or microvascular proliferation does not influence survival of patients with anaplastic oligodendroglial tumours: review of 98 patients.

Accurate prognosis for patients with anaplastic oligodendroglial gliomas is increasingly difficult to make. Characterisation of these tumours remains challenging, increasing proportions of oligodendroglial diagnoses in gliomas are reported, and no WHO 2000 grade IV exists for them, so that highly anaplastic tumours can only be grouped with glioblastoma (GBM) or with grade III oligodendroglioma, which have differing clinical behaviour. Longer survival times reported for patients with glioblastoma containing an oligodendroglial element (GBMO) suggest that a grade IV for oligodendroglial tumours might exist. In patients with anaplastic gliomas containing an oligodendroglial element, we explored whether microvascular proliferation (MVP) and necrosis were associated with shorter survival, sufficient to create a grade IV. Biopsies for 98 patients with anaplastic oligodendroglioma, anaplastic oligoastrocytoma or tumours with an oligodendroglial and GBM element, discharged 1998-2004, were identified from databases at three allied neurosurgery units. Pathology reports were reviewed for the presence of MVP and necrosis. Anaplastic oligoastrocytoma and GBMO were combined to measure the effect of an astrocytic element on survival. For anaplastic oligodendroglioma patients, median survival time was 24 months, while for anaplastic oligoastrocytoma or GBMO patients, it was 9 months. Age 60 or over (P=0.006) and astrocytic element (P=0.01) were the only independent predictors of survival. Patients 60 and over with an astrocytic element had 4.6 times the risk of death of patients under 60 with anaplastic oligodendroglioma.A grade IV cannot be created using necrosis or MVP since neither feature predicted survival after adjustment for age and an astrocytic element. However age and an astrocytic element were strong predictors of poorer survival in patients with anaplastic oligodendroglial tumours.

Age Factors↗

PubMed2005

Multiple cerebral and leptomeningeal metastases from ovarian carcinoma: unusual early presentation.

Although virtually any systemic malignancy is capable of metastasizing to the brain, ovarian carcinoma, one of the more common female genital malignancies, is one of the rarer forms of brain metastases. In general, the outcome for ovarian carcinoma with brain metastases is extremely poor as most of these patients have widespread lesions elsewhere. This report describes the first known case of multiple cerebral and leptomeningeal metastases as the initial manifestation of ovarian carcinoma in a 41-year old woman who presented with a one-week history of headache, vomiting and confusion. CT scan of the brain was unremarkable, but lumbar puncture revealed atypical cells in the CSF. MRI scan of the brain showed multiple small enhancing lesions. Craniotomy for excision of one of these lesions demonstrated metastatic adenocarcinoma. A large ovarian tumour identified on pelvic CT scan was resected and the patient subsequently received chemotherapy and radiotherapy. Unfortunately she continued to decline and died within six months. Unlike primary tumours such as malignant melanoma, ovarian carcinoma does not have a predilection for the central nervous system (CNS), but the rare instances with CNS involvement occur at an advanced stage of the disease. Once the CNS is involved, the outcome is abysmal, even with multimodality therapy. It is extremely unusual for ovarian carcinoma to present with multiple CNS involvement.

Adult↗

PubMed2005

What progress has been made in surgical management of patients with astrocytoma and oligodendroglioma in Australia over the last two decades?

BACKGROUND: Most primary brain cancers are associated with a dismal prognosis because of their aggressive behaviour and high mortality. Surgical resection with adjuvant radiotherapy is a major treatment for these cancers but little has been published about their surgical management in Australia. OBJECTIVE: To determine changes since 1977 in demographic characteristics, tumour frequencies, surgical management, morbidity and survival for 1,339 patients discharged with astrocytoma (A) and oligodendroglioma (O), which comprise the majority of primary brain cancers, recorded prospectively in northern Sydney neurosurgery databases. Discharges were grouped into eras reflecting changes in diagnostic and surgical technology. RESULTS: Between eras 1977-79 and 1999-2002, mean age increased by 9.5 years, and inpatient stay fell from 21 to 9 days. The proportion of O rose as A fell. Of 144 re-biopsies, 16% had less anaplastic pathology, 54% the same and 30% more anaplastic pathology than the first biopsy. Stereotactically assisted surgery increased, with overall rates of burr hole for biopsy decreasing and of craniotomy rising. Between 1980-86 and 1999-2002, inpatient mortality declined from 7.3 to 2.3% of discharges, reopening of craniotomy and wound complication rates fell, while postoperative neurological deficit rose. Deep vein thrombosis and pulmonary embolism rates for discharges increased significantly. Age and histopathologic grade were predictors of survival from 1980. Sex and era of diagnosis did not influence survival. After adjustment for age using proportional hazards regression, survival improved only for anaplastic A, with a 60% improvement for patients diagnosed in era 3, and a 50% improvement for patients diagnosed in era 4 relative to those in era 1. CONCLUSIONS: Although markers of inpatient care have improved since the 1980s, age-adjusted survival has not increased except for patients with anaplastic A.

Astrocytoma↗

PubMed2005

Highly conserved regulatory elements around the SHH gene may contribute to the maintenance of conserved synteny across human chromosome 7q36.3.

Comparative genomic analysis reveals an exceptionally large section of conserved shared synteny between the human 7q36 chromosomal region and the pufferfish (Fugu rubripes) genome. Remarkably, this conservation extends not only to gene order across 16 genes, but also to the position and orientation of a number of prominent conserved noncoding elements (CNEs). A functional assay using zebrafish has shown that most of the CNEs have reproducible and specific enhancer activity. This enhancer activity is often detected in a subset of tissues which reflect the endogenous expression pattern of a proximal gene, though some CNEs may act over a long range. We propose that the distribution of CNEs, and their probable association with a number of genes throughout the region, imposes a critical constraint on genome architecture, resulting in the maintenance of such a large section of conserved synteny across the vertebrate lineage.

Animals↗

PubMed2005

Risk factors and prophylaxis for deep venous thrombosis in neurosurgery.

Acceptance is increasing for pharmacological prophylaxis against deep vein thrombosis (DVT) and pulmonary embolism (PE) for most types of surgery, but its use remains controversial in neurosurgical patients because of the threat of catastrophic hemorrhage. Consequently, mechanical measures such as sequential calf compression and graduated compression stockings are currently the preferred prophylaxis for neurosurgical patients. However, some patients remain at high risk despite these measures and may require prophylaxis with low molecular weight heparins or unfractionated heparin. In neurosurgical patients, known risk factors for DVT or PE include advanced age, malignancy, limb weakness, prolonged surgery, and cranial as opposed to spinal surgery. Using comprehensive neurosurgery databases, the authors identify more specific neurosurgical diagnoses and procedures as risk factors for DVT and PE, and show increases in the frequency of DVT and PE for the wider neurosurgery population and for glioma patients over time. DVT prophylaxis is compared in public and private hospital settings. This chapter contributes to the changing picture of DVT and PE in neurosurgical patients over the last two decades.

Anticoagulants↗

PubMed2004

Highly conserved non-coding sequences are associated with vertebrate development.

In addition to protein coding sequence, the human genome contains a significant amount of regulatory DNA, the identification of which is proving somewhat recalcitrant to both in silico and functional methods. An approach that has been used with some success is comparative sequence analysis, whereby equivalent genomic regions from different organisms are compared in order to identify both similarities and differences. In general, similarities in sequence between highly divergent organisms imply functional constraint. We have used a whole-genome comparison between humans and the pufferfish, Fugu rubripes, to identify nearly 1,400 highly conserved non-coding sequences. Given the evolutionary divergence between these species, it is likely that these sequences are found in, and furthermore are essential to, all vertebrates. Most, and possibly all, of these sequences are located in and around genes that act as developmental regulators. Some of these sequences are over 90% identical across more than 500 bases, being more highly conserved than coding sequence between these two species. Despite this, we cannot find any similar sequences in invertebrate genomes. In order to begin to functionally test this set of sequences, we have used a rapid in vivo assay system using zebrafish embryos that allows tissue-specific enhancer activity to be identified. Functional data is presented for highly conserved non-coding sequences associated with four unrelated developmental regulators (SOX21, PAX6, HLXB9, and SHH), in order to demonstrate the suitability of this screen to a wide range of genes and expression patterns. Of 25 sequence elements tested around these four genes, 23 show significant enhancer activity in one or more tissues. We have identified a set of non-coding sequences that are highly conserved throughout vertebrates. They are found in clusters across the human genome, principally around genes that are implicated in the regulation of development, including many transcription factors. These highly conserved non-coding sequences are likely to form part of the genomic circuitry that uniquely defines vertebrate development.

Animals↗

PubMed2004

Prophylaxis for deep venous thrombosis in neurosurgical oncology: review of 2779 admissions over a 9-year period.

OBJECT: Management of disease in patients undergoing neurosurgical treatment for tumors requires balancing the competing risks of hemorrhage and thrombosis. The authors compared the incidence of clinically apparent deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients admitted for treatment of intracranial and spinal tumors at three institutions. At the public hospital (the Royal North Shore Hospital [RNSH]) nonsequential calf compression was used, and at the other two private neurosurgery services sequential calf compression with low-molecular-weight heparin was used in patients undergoing spinal surgery. All patients wore compression stockings and underwent follow-up scanning after surgery. METHODS: The authors identified from their neurosurgery databases 2779 discharges of patients with tumor from the RNSH and private hospitals between January 1, 1995 and December 31, 2003. Patient admissions were relatively well matched for age, sex, duration of stay, and tumor type. For patients who underwent spinal surgery, the incidence of DVT was higher in the RNSH (2.6% of admissions) than in private hospitals, where no case of DVT was seen (p = 0.02). The incidence of PE was higher in admissions patients who had been treated for cranial tumors in the RNSH (2.9%) than in those treated in the private hospitals (1.3%, p = 0.01). Possible reasons for these discrepancies include a higher proportion of ambulatory patients before and after surgery in the group treated at private hospitals. More emergency and semi-emergency surgery was performed in the RNSH than in the private hospitals. Nevertheless, fewer patients discharged from the RNSH had undergone surgery, which is a known risk factor for DVT. CONCLUSIONS: Patients with intracranial tumors had a higher incidence of PE than those with spinal tumors. The incidence of DVT and PE was higher in patients admitted to the public hospital. The incidence of DVT in patients undergoing spinal procedures was lower when low-molecular-weight heparin was used judiciously, but the incidence of PE in patients undergoing cranial procedures was lower with the private hospital protocol, which did not include prophylaxis with anticoagulating agents.

Anticoagulants↗

PubMed2004

Haemorrhagic brain metastasis from a thymic carcinoma.

Brain metastasis from thymic carcinoma is extremely rare, and there is still no consensus regarding the best management of thymic metastasis to the central nervous system. Here, we report the first-known Australian case. A review of the current literature and the characteristics of thymic tumours with brain metastasis indicate that aggressive management may be able to improve long-term outcomes for these patients. A 49-year-old man presented 2 weeks after thoracotomy for thymic carcinoma resection with a 2-day history of headache, right-sided weakness and expressive dysphasia. CT and MR scans revealed two metastatic brain lesions, one within the left frontal lobe with cystic necrosis and haemorrhage, the other deep in the parietal lobe adjacent to the left ventricle with a lesser degree of haemorrhage. The patient underwent frameless stereotactic craniotomy for excision of the frontal lesion. Histopathology confirmed poorly differentiated thymic carcinoma. Post-operatively his weakness and speech improved dramatically, and he was discharged home within a week, with radiotherapy and chemotherapy to follow. However, he represented with rapidly worsening symptoms and died within a week. Thymic carcinoma is a rare tumour, displaying malignant features clinically and histopathologically with local invasion to adjacent organs. Metastasis is predominantly to lung, bone, liver and kidney, with less predilection for the central nervous system. Treatment for thymic carcinoma is multimodal, but outcome remains poor and life expectancy is very short when brain metastasis with haemorrhage is present.

Brain Neoplasms↗

PubMed2004

A quarter of a century of neurosurgery: the value of a relational database to document trends in neurosurgical practice of a tertiary referral hospital.

OBJECTIVE AND IMPORTANCE: Increasing interest in evidence-based medicine has created a demand for accurate and accessible information on activity and trends in clinical practice. A database of all neurosurgery admissions at a teaching hospital maintained by a scientist has been utilised to examine changes in practice and complications from 1977 to 2001. METHODS: A relational database, set up in 1982, now contains an unbroken record of all neurosurgical admissions at Royal North Shore Hospital (RNSH) since 1976. It supplies information for morbidity and mortality meetings, research and administrative purposes. A total of 23,766 admissions from 1977 to 2001 were examined. Statistical analysis of trends in age, gender, length of stay (LOS), diagnostic mix, surgery rates and complications in admissions was based on diagnostic groupings. RESULTS: Proportions of vascular admissions rose and of trauma admissions fell. Mean age increased significantly for tumour, trauma and spinal patients; geometric mean LOS declined significantly for tumour, spine, vascular, cranial nerve and peripheral nerve groups. Concurrently, inpatient death rate fell significantly for tumour and vascular patients. Deep vein thrombosis (DVT) rose significantly for trauma, vascular, tumour, spinal and infection patients; pulmonary embolism (PE) rose significantly for tumour, trauma and spinal patients. There was no significant change in wound infection rate at approximately 3.5% of all operated patients. Wound haematoma rates fell significantly from 4.0% to 2.9% while the rate of postoperative cerebrospinal fluid (CSF) leak rose significantly from 0.5% to 2.0% of all operated patients. CONCLUSION: The value of the database is demonstrated by its ability to provide analysis which shows statistically significant changes over time. Declining death rate and LOS indicate improved efficiency in managing patients, but these are offset by rising rates of CSF leak, DVT and PE. Such rises reflect the changing patterns of casemix and surgery performed, and increasing financial pressures on hospital departments.

Adult↗

PubMed2002

Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes.

The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some "giant" genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match to Fugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.

Animals↗

PubMed2002

Analyses of the extent of shared synteny and conserved gene orders between the genome of Fugu rubripes and human 20q.

Cosmid and BAC contig maps have been constructed across two Fugu genomic regions containing the orthologs of human genes mapping to human chromosome 20q. Contig gene contents have been assessed by sample sequencing and comparative database analyses. Contigs are centered around two Fugu topoisomerase1 (top1) genes that were initially identified by sequence similarity to human TOP1 (20q12). Two other genes (SNAI1 and KRML) mapping to human chromosome 20 are also duplicated in Fugu. The two contigs have been mapped to separate Fugu chromosomes. Our data indicate that these linkage groups result from the duplication of an ancestral chromosome segment containing at least 40 genes that now map to the long arm of human chromosome 20. Although there is considerable conservation of synteny, gene orders are not well conserved between Fugu and human, with only very short sections of two to three adjacent genes being maintained in both organisms. Comparative analyses have allowed this duplication event to be dated before the separation of Fugu and zebrafish. Our data (which are best explained by regional duplication, followed by substantial gene loss) support the hypothesis that there have been a large number of gene and regional duplications (and corresponding gene loss) in the fish lineage, possibly resulting from a single whole genome duplication event.

Animals↗