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Biomedical subjects

B Cooke

Publications and source records attributed to B Cooke.

At least 19 recordsLinked to original sources
PubMed2005

The inadvertent introduction into Australia of Trypanosoma nabiasi, the trypanosome of the European rabbit (Oryctolagus cuniculus), and its potential for biocontrol.

Wild rabbits (Oryctolagus cuniculus) in Australia are the descendents of 24 animals from England released in 1859. We surveyed rabbits and rabbit fleas (Spilopsyllus cuniculi) in Australia for the presence of trypanosomes using parasitological and PCR-based methods. Trypanosomes were detected in blood from the European rabbits by microscopy, and PCR using trypanosome-specific small subunit ribosomal RNA (SSU rRNA) gene primers and those in rabbit fleas by PCR. This is the first record of trypanosomes from rabbits in Australia. We identified these Australian rabbit trypanosomes as Trypanosoma nabiasi, the trypanosome of the European rabbit, by comparison of morphology and SSU rRNA gene sequences of Australian and European rabbit trypanosomes. Phylogenetic analysis places T. nabiasi in a clade with rodent trypanosomes in the subgenus Herpetosoma and their common link appears to be transmission by fleas. Despite the strict host specificity of trypanosomes in this clade, phylogenies presented here suggest that they have not strictly cospeciated with their vertebrate hosts. We suggest that T. nabiasi was inadvertently introduced into Australia in the 1960s in its flea vector Spilopsyllus cuniculi, which was deliberately introduced as a potential vector of the myxoma virus. In view of the environmental and economic damage caused by rabbits in Australia and other islands, the development of a virulent or genetically modified T. nabiasi should be considered to control rabbits.

Animals↗
PubMed2003

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study.

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC ) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC.

Adult↗
PubMed2002

Inflammation is associated with progression of actinic keratoses to squamous cell carcinomas in humans.

BACKGROUND: Squamous cell carcinoma (SCC) is a common skin tumour that may metastasize and lead to death. We have observed that before actinic keratoses (AK) progress to SCCs they may become tender and inflamed. In some of these, histological examination shows that they are, in fact, SCCs. OBJECTIVES: To study the progression of AK to SCCs. METHODS: We studied skin tumours from 50 patients with either asymptomatic AK, inflamed AK or SCCs, using immunocytochemistry. The diagnosis of each tumour was confirmed by histological examination. RESULTS: Studies of differentiation using heat shock protein 27 showed a stepwise loss of differentiation as the tumours progressed from asymptomatic AK, through inflamed AK to SCCs. During the inflamed AK phase, there was a marked increase in T lymphocytes and Langerhans cells: the number of infiltrating cells diminished as progression to SCC occurred. There was an increase in immunoreactive p53 and the apoptosis inhibitor bcl-2 as tumours progressed from AK to SCCs, and a decrease in Fas and Fas ligand. CONCLUSIONS: These studies have shown that progression from benign to malignant tumours may be associated with an inflammatory response, which appears to drive malignant conversion, but subsides rapidly following this conversion.

Adult↗
PubMed2002

First synthesize new viruses then regulate their release? The case of the wild rabbit.

European wild rabbits originated in southwestern Europe but have been introduced into many other countries world-wide, becoming serious pests in many instances. As a consequence of rabbits being regarded so differently, applied research for their management often has opposing goals, namely their conservation or their control. Furthermore, modern gene technology has led to the concept of using genetically modified myxoma viruses for rabbit management, again with quite contrary aims in mind. In this paper we explain the possible ecological and economic consequences of using these genetically modified viruses inappropriately and we consider whether national and international regulations are sufficient to prevent improper use. If international regulations are inadequate, molecular biologists and ecologists must consider the consequences of their research and advice beyond their own country to avoid unwanted impacts.

Animals↗
PubMed2001

Intrathecal hydromorphone for chronic nonmalignant pain: a retrospective study.

OBJECTIVE: Ten percent to 15% of patients with chronic pain experience intolerable side effects or inadequate analgesia with continuous intrathecal morphine therapy. Although clinical experience suggests that rotation to hydromorphone (Dilaudid) can reduce side effects and recapture analgesia, there have been only scattered reports of long-term intrathecal hydromorphone use in patients with nonmalignant pain. The purpose of this study is to review the safety and effectiveness of continuous intrathecal hydromorphone in the management of patients with nonmalignant pain in whom continuous intrathecal morphine therapy has failed. DESIGN: A retrospective review of 37 patients with chronic nonmalignant pain managed with intrathecal hydromorphone after failure of intraspinal morphine. RESULTS: The mean age of patients was 64 years +/- 12 SD. All patients suffered from severe nonmalignant pain, most from failed lumbosacral spine operations (19/37; 51%). Morphine was replaced with hydromorphone because of pharmacological complications (21/37; 57%) or inadequate analgesic response (16/37; 43%) after an average of 11 months +/- 11 SD of intrathecal therapy. Pharmacological complications, particularly nausea and vomiting, pruritus, and sedation were reduced by hydromorphone in most patients. Peripheral edema was improved by hydromorphone but tended to recur with prolonged hydromorphone exposure. Analgesic response was improved by at least 25% in six of 16 patients who were switched to hydromorphone because of poor pain relief. CONCLUSIONS: Hydromorphone can be a safe, analgesic alternative for long-term intrathecal management of nonmalignant pain among patients in whom morphine fails because of pharmacological side effects or inadequate pain relief.

Journal Article↗
PubMed2001

Neurological complications of cervical spine manipulation.

To obtain preliminary data on neurological complications of spinal manipulation in the UK all members of the Association of British Neurologists were asked to report cases referred to them of neurological complications occurring within 24 hours of cervical spine manipulation over a 12-month period. The response rate was 74%. 24 respondents reported at least one case each, contributing to a total of about 35 cases. These included 7 cases of stroke in brainstem territory (4 with confirmation of vertebral artery dissection), 2 cases of stroke in carotid territory and 1 case of acute subdural haematoma. There were 3 cases of myelopathy and 3 of cervical radiculopathy. Concern about neurological complications following cervical spine manipulation appears to be justified. A large long-term prospective study is required to determine the scale of the hazard.

Adult↗
PubMed2000

Falciparum malaria: sticking up, standing out and out-standing.

Cytoadherence is believed to be fundamental for the survival of Plasmodium falciparum in vivo and, uniquely, is a major determinant of the virulence of this parasite. Despite the widely professed importance of cytoadhesion in the development of severe disease, there are a number of aspects of this highly complex process that remain poorly understood. Recent progress in the understanding of cytoadhesive phenomena was discussed extensively at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000. Here, Brian Cooke, Mats Wahlgren and Ross Coppel consider just how far we have progressed during the past 30 years and highlight what is still missing in our understanding of the mechanisms and clinical relevance of this apparently vital process.

Animals↗
PubMed2000

Metastatic secretory breast cancer. Non-responsiveness to chemotherapy: case report and review of the literature.

Secretory carcinoma of the breast is a rare and indolent tumour originally described in children but occurring equally in the adult population. The principal management problems following primary surgical treatment are local recurrence and axillary lymph node metastases. Distant metastases are extremely rare. We present the case of a 27-year-old woman with pulmonary metastases from a secretory breast cancer treated by mastectomy and axillary lymph node dissection 12 years previously. There was no response to chemotherapy; however, the patient remained alive and active two years from presentation with metastatic disease and one year from cessation of all cytotoxic chemotherapy. She eventually died of respiratory failure two and a half years after presentation. To our knowledge, this is only the fourth reported case of distant metastases from secretory breast cancer and the second reported case in which current active chemotherapy has been used. We review the literature and discuss the apparent chemoresistance of this tumour including the lack of membrane staining for Her2/neu. In the absence of any proven effective chemotherapy we believe that symptom control becomes the focus of management and offers patients with metastatic secretory breast cancer the greatest chance of a functional and good quality existence.

Adult↗
PubMed2000

Cytokine profiles in spontaneously regressing basal cell carcinomas.

BACKGROUND: Basal cell carcinomas (BCCs) can cause considerable morbidity due to their ability to enlarge progressively and to destroy underlying tissues. However, some BCCs may undergo spontaneous regression in the absence of therapy capable of inducing antineoplastic effects. Histological criteria for this process have been described, and previous studies have suggested that it may be mediated by infiltrating activated CD4-positive T cells. OBJECTIVES: The purpose of this study was to compare the expression of cytokines in actively regressing and non-regressing BCCs, to ascertain if active regression is associated with a particular cytokine profile. METHODS: Reverse transcriptase-polymerase chain reaction, a sensitive, quantitative technique allowing analysis of multiple cytokines from small tumour samples, was used. RESULTS: Interferon (IFN)-gamma was significantly elevated in actively regressing BCCs compared with non-regressing BCCs. Furthermore, interleukin (IL)-2, tumour necrosis factor (TNF)-beta and CD3 delta tended to be elevated in actively regressing tumours, although not to statistically significant levels. IFN-gamma, IL-2, IL-10, TNF-beta, granulocyte-macrophage colony-stimulating factor and Fas ligand showed strong positive correlations with CD3 delta, indicating an association between infiltrating T cells and these cytokines. CONCLUSIONS: These findings support a role for T-helper 1 type cytokines in mediating spontaneous regression of BCCs.

CD3 Complex↗
PubMed2000

Aromatherapy: a systematic review.

Aromatherapy is becoming increasingly popular; however there are few clear indications for its use. To systematically review the literature on aromatherapy in order to discover whether any clinical indication may be recommended for its use, computerised literature searches were performed to retrieve all randomised controlled trials of aromatherapy from the following databases: MEDLINE, EMBASE, British Nursing Index, CISCOM, and AMED. The methodological quality of the trials was assessed using the Jadad score. All trials were evaluated independently by both authors and data were extracted in a pre-defined, standardised fashion. Twelve trials were located: six of them had no independent replication; six related to the relaxing effects of aromatherapy combined with massage. These studies suggest that aromatherapy massage has a mild, transient anxiolytic effect. Based on a critical assessment of the six studies relating to relaxation, the effects of aromatherapy are probably not strong enough for it to be considered for the treatment of anxiety. The hypothesis that it is effective for any other indication is not supported by the findings of rigorous clinical trials.

Anxiety↗
PubMed1999

Regression of melanoma, but not keratoacanthoma, is associated with increased HLA-B22 and decreased HLA-B27 and HLA-DR1.

Sixty three Caucasian patients with either melanoma, keratoacanthoma or squamous cell carcinoma were human leucocyte antigen (HLA) typed. The regressing tumour groups were compared with their non-regressing counterparts, and the patient groups were compared with a control Caucasian population. Melanoma patients showing histological regression were more likely to be HLA-B22 positive, and HLA-B27 and -DR1 negative, than those without features of regression. When compared with a control population, the group of melanoma patients were more likely to be HLA-B22 positive. Comparison of the group of keratoacanthomas, a self-regressing tumour, and the group of squamous cell carcinomas, a non-regressing tumour, did not show any significant differences in HLA typing.

Carcinoma, Squamous Cell↗
PubMed1999

Heart rate variability and plasma catecholamines in patients during opioid detoxification.

It has been shown that rapid opioid detoxification is associated with increased sympathetic activity (SYMP) and plasma catecholamines. Heart rate (HR) variability may provide a noninvasive method of evaluating withdrawal and sympathetic activation caused by the reversal of opioid binding in patients who are opioid dependent. The purpose of this study was to evaluate the relationship between HR variability and plasma catecholamines during opioid detoxification. Patients were anesthetized with propofol, intubated, paralyzed with rocuronium infusion, and ventilated. The bispectral index (BIS) of the electroencephalogram was recorded with the patient awake as well as during propofol anesthesia. SYMP was determined by power spectral analysis of HR variability. Plasma epinephrine and norepinephrine were measured at baseline propofol anesthesia and during naltrexone treatment in eight opioid-dependent patients. Nonopioid-dependent controls (n = 7) were monitored during surgery without naltrexone treatment or measurement of plasma catecholamines. Compared with an awake status, propofol anesthesia significantly decreased the BIS and SYMP in both groups of patients. Controls showed no change from baseline anesthetized levels during surgery. Plasma norepinephrine and epinephrine as well as SYMP increased 300 to 400% (P < .05) during naltrexone treatment in opioid-dependent patients, and the time to peak increase in plasma norepinephrine correlated with the increase in SYMP (r = 0.89, P < .01). These results confirm that opioid detoxification increases plasma catecholamines and SYMP in a similar manner. HR rate variability may provide a low-cost real-time noninvasive method of evaluating the reversal of opioid binding in opioid-dependent patients.

Adult↗
PubMed1999

Efficacy of transverse tripolar stimulation for relief of chronic low back pain: results of a single center.

The goal of this study was to evaluate the efficacy of the transverse tripolar spinal cord stimulation system (TTS) in providing relief of low back pain in patients with chronic non-malignant pain. Transverse tripolar electrodes were implanted in the lower thoracic region (T(8-9) to T(12)-L(1)) in 10 patients with chronic neuropathic pain, all of whom reported a significant component of low back pain in combination with unilateral or bilateral leg pain. One patient reported inadequate pain relief during the trial and was not implanted with a permanent generator. A visual analogue scale of low back pain showed a nonsignificant decrease from 64 +/- 19 to 47 +/- 30 (p = 0.25; paired t test) after 1 month of stimulation. Similarly, functional disability evaluated using Oswestry Low Back Pain Questionnaire was not improved (p = 0. 46; paired t test). We conclude that chronic low back pain is not particularly responsive to the transverse stimulation provided by the TTS system.

Adult↗
PubMed1998

Sexual differentiation of the vertebrate brain: principles and mechanisms.

A wide variety of sexual dimorphisms, structural differences between the sexes, have been described in the brains of many vertebrate species, including humans. In animal models of neural sexual dimorphism, gonadal steroid hormones, specifically androgens, play a crucial role in engendering these differences by masculinizing the nervous system of males. Usually, the androgen must act early in life, often during the fetal period to masculinize the nervous system and behavior. However, there are a few examples of androgen, in adulthood, masculinizing both the structure of the nervous system and behavior. In the modal pattern, androgens are required both during development and adulthood to fully masculinize brain structure and behavior. In rodent models of neural sexual dimorphism, it is often the aromatized metabolites of androgen, i.e., estrogens, which interact with estrogen receptors to masculinize the brain, but there is little evidence that aromatized metabolites of androgen play this role in primates, including humans. There are other animal models where androgens themselves masculinize the nervous system through interaction with androgen receptors. In the course of masculinizing the nervous system, steroids can affect a wide variety of cellular mechanisms, including neurogenesis, cell death, cell migration, synapse formation, synapse elimination, and cell differentiation. In animal models, there are no known examples where only a single neural center displays sexual dimorphism. Rather, each case of sexual dimorphism seems to be part of a distributed network of sexually dimorphic neuronal populations which normally interact with each other. Finally, there is ample evidence of sexual dimorphism in the human brain, as sex differences in behavior would require, but there has not yet been any definitive proof that steroids acting early in development directly masculinize the human brain.

Animals↗
PubMed1998

The initial impact of rabbit hemorrhagic disease on European rabbit populations in South Australia.

The calicivirus agent for rabbit hemorrhagic disease (RHD) escaped from an island quarantine station to the Australian mainland in October 1995. Within 2 wk it was detected at an established field study site where wild European rabbits (Oryctolagus cuniculus) were being monitored in the Flinders Ranges National Park (South Australia, Australia). During November 1995, RHD reduced the rabbit numbers on the site by 95%. Approximately 3% of the population survived challenge by RHD and developed antibodies. Most of the antibody-positive survivors were 3- to 7-wk-old when challenged. Many rabbits died underground, but counts of rabbit carcasses found on the surface indicated that approximately 1 million rabbits had died above ground in the National Park, and that > 30 million rabbits may have died in adjacent areas during the November epidemic.

Age Distribution↗
PubMed1996

Chemokines and T lymphocyte recruitment to lymph nodes in HIV infection.

Recruitment of T lymphocytes to lymph nodes in patients with HIV infection is critical to the pathogenesis of disease. Chemokines are a family of cytokines, which are potent regulators of leukocyte migration. We studied the leukocyte populations and expression of chemokines known to be active upon T cells in lymph nodes of four HIV infected patients and seven control subjects using in situ hybridization, immunohistochemistry, and FACS analysis. The HIV lymph nodes showed CD8+ T lymphocyte accumulation and strongly enhanced chemokine expression, notably for the CD8+ T cell chemoattractant, macrophage inflammatory protein (MIP)-1 alpha. Resident macrophages appeared to be a major cellular source of chemokines in the HIV nodes. RANTES expression was present in both HIV and control lymph nodes, suggesting a physiological role for this chemokine in T lymphocyte recirculation. Chemokines may be important determinants of T lymphocyte accumulation in lymphoid tissue of patients with HIV/AIDS.

Adult↗