Medicine at the 2000 Sydney Olympic Games: the New Zealand health team.
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Australia↗
Biomedical subjects
D Robinson
Publications and source records attributed to D Robinson.
The risk of subsequent primary cancers after colorectal cancer in southeast England.
BACKGROUND: Multiple cancers may occur in an individual because of a genetic predisposition, environmental exposure, cancer therapy, or immunological deficiency. Colorectal cancer is one of the most commonly diagnosed cancers, and inherited factors play an important role in its aetiology. AIMS: To characterise the occurrence of multiple primary cancers in patients diagnosed with colorectal cancer and explore the possibility of a common aetiology for different cancer sites. PATIENTS: The Thames Cancer Registry database was used to identify patients with a first colorectal cancer, resident in the North or South Thames region, diagnosed between 1 January 1961 and 31 December 1995. A total of 127 281 patients were included, 61 433 men and 65 848 women. METHODS: Observed numbers of cancers occurring after the diagnosis of colorectal cancer were compared with expected numbers, calculated using appropriate age, sex, and period specific rates, to obtain standardised incidence ratios. The occurrence of colorectal cancers subsequent to cancers at other sites was also examined. RESULTS: Small intestinal cancer was significantly increased in men diagnosed with colorectal cancer before the age of 60 years and in women diagnosed with colorectal cancer after the age of 65 years. Colorectal cancer was also significantly increased after a first diagnosis of cancer of the small intestine. Other cancer sites with a significant increase after colorectal cancer included the cervix uteri, corpus uteri, and ovary. CONCLUSIONS: Patients with colorectal cancer are at increased risk of developing cancer at a number of other sites. Some of these associations are consistent with the effects of known inherited cancer susceptibility genes.
Adult↗
Mechanical resistance of biological repair cartilage: comparative in vivo tests of different surgical repair procedures.
The former common knowledge that cartilage lesions do not heal has been modified over the last few years due to new technologies. For repair of deeper circumscribed lesions osteochondral press-fit grafting and tissue engineering are used in clinical application. The histological data of the hyaline-like tissue obtained by engineering are just as satisfactory as the surviving grafted hyaline cartilage on top of osteochondral cylinders. But comparative studies are still lacking. To fill the gap and with a view to repairing larger osteoarthritic defects we have performed an in vivo study on 16 goats. Three months after the creation of a full thickness wide cartilage defect on the femoral condyle with harvesting of cartilage samples for tissue cultures we performed secondary cartilage repair procedures on the installed osteoarthritis areas: 1) grafting with autogenic osteochondral press-fit cylinders from the opposite knee, 2) autologous engineered chondrocyte grafting under periosteal flaps, 3) both in combination. The harvesting defects were either left as controls or filled with a hyaluronate fleece. After eight months the repaired areas and the harvesting defects were examined for cartilage stiffness as a novel comparative parameter. Compared to normal the cartilage on top of osteochondral grafts is considerably stiffer. Engineered cartilage is weaker than normal. Spontaneously ingrown fibrous cartilage is much weaker even with a carrier fleece. A combination of osteochondral press-fit grafts with engineered autologous cells restores biomechanical qualities to repaired larger degenerative cartilage defects.
Animals↗
Transient bone oedema of the tibia mimicking a tumorous process.
The authors describe a distinct clinical entity consisting of bony tenderness, increased isotope uptake along the metaphyses and/or diaphyses and magnetic resonance changes simulating a bone marrow-replacing lesion. Bone biopsies indicate the presence of bone marrow fibrosis and some new bone formation. Nine such cases were prospectively evaluated according to a standardized protocol including clinical examination, x-rays, bone scan and CT scan as well as MRI scans including contrast medium injection. All patients presented with tibial tenderness. In one case the bone was noticeably thicker as compared to the other side. The ages ranged from 6 years to 64 years and 6 of the patients were female. Xrays were normal in 6/9 patients; the rest had minimal periosteal reaction, and mild intramedullary sclerosis. Uniform imaging findings were longitudinal increased uptake along the metadiaphysis of the tibia on bone scans, and increased bone marrow density on CAT scans without a fracture line. A magnetic resonance study indicated bone marrow replacement as demonstrated by an area of low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Some enhancement of signal was observed following gadolinium injection. This clinical entity, which the authors attribute to be a medullary stress reaction, is self-limited, and pain resolves within 3 months. However the radiographic changes appear to be permanent. A biopsy is not required provided no cortical penetration or soft tissue mass is demonstrated by MRI scan.
Adolescent↗
[Obligatory and facultative symptoms of the Alice in wonderland syndrome].
The Alice in Wonderland syndrome (AIWS), as described by Todd in 1955, denotes a variety of self-experienced paroxysmal body schema disturbances (obligatory core symptoms of the AIWS) which may co-occur with depersonalization, derealization, visual illusions and disorders of the time perception (facultative symptoms of the AIWS). The name comes, of course, from Lewis Carroll's 1865 novel "Alice's Adventures in Wonderland", which is believed to have been inspired by Carroll's own migraine experiences documented as early as 1856. Recent studies of the AIWS occurring as somesthetic migraine aura indicated that the body schema disturbance of macrosomatognosia most frequently affects the head and upper extremities, paralleling the extension of their representation in the human brain. As a misapprehension commonly encountered in the medical literature, it has been suggested to define the AIWS by the presence of visual rather than somesthetic perceptual disturbances, e.g. metamorphopsia and/or visual hallucinations, but this change and broadening of Todd's definition of the AIWS turns it to a both scientifically and clinically useless concept.
Hallucinations↗
Cancer risks in women with 2 breast or ovarian cancers: clues to genetic cancer susceptibility.
Women diagnosed with 2 cancers of the breast and/or ovary are at higher risk of developing subsequent cancers. Using registrations from the Thames Cancer Registry, we quantified the risks at different cancer sites. Increased risks were found for cancers that are part of the BRCA1 and BRCA2 tumour spectrum: oropharyngeal cancer, malignant melanoma of the skin (BRCA2) and colon cancer (BRCA1). We also found significantly increased risks of myeloid leukaemia (probably due to radiotherapy) and of cancer of the corpus uteri (which may be due to hormonal factors).
Breast Neoplasms↗
MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway.
In this study, we report the cloning and characterization of a novel human Ste20-related kinase that we designated MST4. The 416 amino acid full-length MST4 contains an amino-terminal kinase domain, which is highly homologous to MST3 and SOK, and a unique carboxy-terminal domain. Northern blot analysis indicated that MST4 is highly expressed in placenta, thymus, and peripheral blood leukocytes. Wild-type but not kinase-dead MST4 can phosphorylate myelin basic protein in an in vitro kinase assay. MST4 specifically activates ERK but not JNK or p38 MAPK in transient transfected cells or in stable cell lines. Overexpression of dominant negative MEK1 or treatment with PD98059 abolishes MST4-induced ERK activity, whereas dominant-negative Ras or c-Raf-1 mutants failed to do so, indicating MST4 activates MEK1/ERK via a Ras/Raf-1 independent pathway. HeLa and Phoenix cell lines overexpressing wild-type, but not kinase-dead, MST4 exhibit increased growth rate and form aggressive soft-agar colonies. These phenotypes can be inhibited by PD98059. These results provide the first evidence that MST4 is biologically active in the activation of MEK/ERK pathway and in mediating cell growth and transformation.
Amino Acid Sequence↗
Longitudinal study of brain morphology in first episode schizophrenia.
BACKGROUND: Beginning with Kraepelin, schizophrenia has been viewed as a progressive disorder. Although numerous studies of the longitudinal course of schizophrenia have demonstrated the clinical deterioration that occurs predominantly in the early stages of the illness, the pathophysiology of this clinical phenomenon has not been established. This aspect of the illness may be of critical importance to understanding the pathogenesis of schizophrenia and determining preventive therapeutic strategies. Abnormalities in brain morphology have been consistently described in schizophrenia, but it is not known when in the natural history of the illness they arise and whether they are progressive. Previous studies of brain morphology have been inconclusive, in part because of the variability of methods for image acquisition and analysis, assessment of patients already at chronic stages of their illness with extensive prior treatment exposure, and inadequate periods of follow-up. METHODS: To address these questions we examined 107 patients in their first episode of schizophrenia or schizoaffective disorder and 20 healthy volunteers using high resolution magnetic resonance imaging (MRI) and clinical assessments of psychopathology and treatment outcome for periods of up to 6 years. Fifty-one patients and 13 control subjects had MRIs after at least 12 months of follow-up. RESULTS: Results confirm the findings of ventricular enlargement and anterior hippocampal volume reductions in first episode schizophrenia patients that have been previously reported. In addition, we found changes in selected structures over time in relation to treatment outcome, including increases in ventricular volume that were associated with poor outcome patients. Contrary to our hypothesis, there were no significant reductions in cortical and hippocampal volumes over time. CONCLUSIONS: The finding of progressive ventricular enlargement in patients with poor outcome schizophrenia is consistent with the hypothesis that persistent positive and negative symptoms result in progressive brain changes in the form of ventricular enlargement, possibly due to neurodegeneration rather than the confounding effects of treatment. Future studies of first episodes of schizophrenia should utilize higher resolution imaging techniques that compare clinically well characterized patients with and without poor outcome and recurrent symptoms to control subjects who are well matched to patients for age and gender. There is also a need to control for treatment effects of typical antipsychotic medication on brain structure.
Adolescent↗
delta(15)N as an integrator of the nitrogen cycle.
Natural abundances of the rare stable isotope of nitrogen, 15N, are now being used widely in research on N cycling in organisms and ecosystems. 15N natural abundances are used in fundamentally different ways from traditional 15N tracers by integrating N cycle processes via N isotope fractionations and the mixing of various N-containing pools. This approach of using 15N natural abundances still requires certain technical and conceptual advances before it can be used routinely in ecological research. Here, the basis of the natural abundance 15N approach and opportunities for applying it in ecology are reviewed, and recent progress towards overcoming some of the key technical problems and in revealing large-scale patterns in N cycle processes is discussed.
Journal Article↗
Antagonists of calcium fluxes and calmodulin block activation of the p21-activated protein kinases in neutrophils.
Neutrophils stimulated with fMLP or a variety of other chemoattractants that bind to serpentine receptors coupled to heterotrimeric G proteins exhibit rapid activation of two p21-activated protein kinases (Paks) with molecular masses of approximately 63 and 69 kDa (gamma- and alpha-Pak). Previous studies have shown that products of phosphatidylinositol 3-kinase and tyrosine kinases are required for the activation of Paks. We now report that a variety of structurally distinct compounds which interrupt different stages in calcium/calmodulin (CaM) signaling block activation of the 63- and 69-kDa Paks in fMLP-stimulated neutrophils. These antagonists included selective inhibitors of phospholipase C (1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione), the intracellular Ca(2+) channel (8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate), CaM (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; N-(4-aminobutyl)-5-chloro-1-naphthalenesulfonamide; trifluoperazine), and CaM-activated protein kinases (N-[2-(N-(chlorocinnamyl)-N:-methylaminomethyl)phenyl]-N-[2-hydroxyethyl]-4-methoxybenzenesulfonamide). This inhibition was dose-dependent with IC(50) values very similar to those that interrupt CaM-dependent reactions in vitro. In contrast, less active analogues of these compounds (1-[6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-2,5-pyrrolidinedione; N-(6-aminohexyl)-1-naphthalenesulfonamide; N-(4-aminobutyl)-1-naphthalenesulfonamide; promethazine; 2-[N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzyl-amine]) did not affect activation of Paks in these cells. CaM antagonists (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; trifluoperazine), but not their less-active analogues (N-(6-aminohexyl)-1-naphthalenesulfonamide; promethazine), were also found to block activation of the small GTPases Ras and Rac in stimulated neutrophils along with the extracellular signal-regulated kinases. These data strongly suggest that the Ca(2+)/CaM complex plays a major role in the activation of a number of enzyme systems in neutrophils that are regulated by small GTPases.
Animals↗
Incidence of multiple primary cancers in a cohort of women diagnosed with breast cancer in southeast England.
Among women in the Thames Cancer Registry database with a first breast cancer diagnosed between 1961-1995 observed numbers of subsequent cancers were compared with expected numbers and standardized incidence ratios were calculated. The occurrence of breast cancers subsequent to cancers at other sites was also examined. Women diagnosed with breast cancer before age 50 had significantly elevated risks for 9 cancer sites namely, oesophagus, stomach, lung, bone, connective tissue, breast, corpus uteri, ovary and myeloid leukaemia compared with 2 sites (corpus uteri and myeloid leukaemia) in women diagnosed at age 50 and above. Some of these associations are consistent with the effects of known inherited cancer susceptibility genes, shared environmental factors, or therapy.
Age Factors↗
Two freezing cycles ensure interface sterilization by cryosurgery during bone tumor resection.
Cryosurgery utilizing an argon-based system allows bone-tumor interface sterilization, while avoiding the risks of conventional cryosurgery. This study was conducted in order to evaluate the number of freezing cycles required for interface sterilization in cases of aggressive human bone tumors. Sixteen tumors were included (six chondrosarcomas, eight metastatic carcinomas, and two giant cell tumors). All occurred within long bones. In all cases a standardized marginal resection was performed. Following thorough curettage, we sampled five different locations within the tumor interface by a cylindrical hollow trephine. The interface viability was assessed using the XTT method. Quantitative histological evaluation was based on the percentage of live cells divided by total lacunae number in five random medium-power fields. One freezing cycle (5 min, -40 degrees C) reduced tumor viability to approximately 5% of prefreezing. However, there were still live specimens. Two or three freezing cycles led to complete interface sterilization. The difference between a single freezing cycle and two freezing cycles was significant (ANOVA, F = 130, P < 0.01). The difference between two freezing cycles and three freezing cycles was not significant (ANOVA, F = 0.14, P < 0.6). The results of the XTT method for the assessment of interface viability correlated well with histological evaluation of the percentage of viable cells (r = 0.89), as well as with cell culture results of frozen vs. prefreezing tumor samples. In conclusion, two freezing cycles are adequate to achieve tumor-bone interface sterilization in aggressive human bone tumors.
Adult↗
Pharmacological management of detrusor instability.
Urinary incontinence and lower urinary tract dysfunction remain an important cause of morbidity, affecting at least 14% of women over the age of 30 years. Whilst the etiology and pathophysiology of detrusor instability remains to be elucidated drug therapy remains important in the management of women with the irritative symptoms of urgency, frequency and urge incontinence. The number of drugs which have been developed illustrates the point that none are ideal, often having systemic adverse effects limiting their therapeutic usage and affecting compliance. This review aims to assess the current pharmacological management of detrusor instability as well as examining recent progress in the development of new agents, some of which may prove to be efficacious.
Adrenergic alpha-Antagonists↗
Image-guided surgery of small breast cancers.
BACKGROUND: Widespread screening mammography has resulted in detection of many breast cancers smaller than one cm. Image-guided percutaneous needle sampling provides accurate diagnostic and prognostic information for adjuvant therapy. Less invasive methods based on imaging techniques are emerging as an alternative to wire localization and lumpectomy. DATA SOURCES: Information presented in this overview was provided by seven investigators from five medical centers in the United States. These researchers are currently developing various techniques of image-guided percutaneous therapy of small (Tis, 1) breast cancers. CONCLUSIONS: Several percutaneous treatment modalities for treatment of early breast cancer, either excisional or in-situ ablative, are described in this overview and their potential applications are discussed.
Biopsy↗
2001 Image-guided percutaneous breast cancer ablation meeting at the American Society of Breast Surgeons.
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Breast Neoplasms↗
The effect of accidental sulphuric acid leaking on metal distributions in estuarine sediment of Patos Lagoon.
In August of 1998 the tanker BAHAMAS belonging to the Chem Oil Company containing 12,000 t of concentrated sulphuric acid, had an accident on board, after which estuarine water entered one of the compartments of the tanker, resulting in a vigorous exothermic reaction. The reaction of acid with the metallic interior hull of the ship and the accompanying heat and H2 production resulted in an imminent risk of explosion. To avoid an explosion, given the fact that neutralization was not possible, some of the cargo was discharged into the surrounding water. Neutralization was done in January 1999, after the acid concentration in the tanker had decreased and the concentrations of Fe, Cr and Ni remained elevated. Metal concentrations in bottom sediments showed significant modifications. Leached mercury migrated and redeposited downstream, reaching approximately 76 times the background values. Such an anomaly has a well expressed barrier character. The mechanism for redeposition of Hg and other metals probably followed the pattern: Downstream as a result of dilution and mixing with seawater the pH of acid-water increases, favouring adsorption and/or precipitation of metals. The leading edge of a geochemical barrier, at positions 7-9 of sampling sites (Fig. 1), is confirmed by pH variations in the water. The reestablishment of normal pH occurred after a short time due to the high buffering capacity of seawater and large natural dilution process. The concentration of metals in estuarine water during and after the accident showed insignificant anomalies.
Adsorption↗
Discovery of the hexosaminidase isoenzymes.
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Animals↗
Abdominal pain and emergency department evaluation.
By approaching the abdominal pain patient in a systematic fashion, the physician can improve his or her performance in evaluating the patient in a safe and efficient manner without extensive or redundant tests.
Abdominal Pain↗