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Biomedical subjects

Brian Kelly

Publications and source records attributed to Brian Kelly.

18 recordsLinked to original sources
PubMed2006

Deterioration of visual acuity associated with growth hormone therapy in a child with extreme short stature and high hypermetropia.

BACKGROUND: Growth hormone (GH) has long been implicated in the pathogenesis of diabetic retinopathy, although its precise role remains ill-defined. In 1998, an association between exogenous human GH and retinal pathology in non-diabetic subjects was described. CASE REPORT: A female child with extreme short stature of unknown aetiology (height -7.38 SD at 11.3 years) and severe hypermetropia developed retinopathy with visual deterioration during two separate empiric trials of GH therapy. On the first occasion, a relatively high dose of GH (10.5 mg/m2/week) administered from age 4.4 to age 4.7 years was associated with the development of central serous retinopathy, resulting in marked reduction in visual acuity. On cessation of GH, the macular oedema resolved, and visual acuity improved. At age 5.6 years, GH therapy was re-introduced at a lower dose (3.9 mg/m2/week) and her vision monitored closely. Bilateral retinal oedema recurred after 3 months, and GH therapy was stopped. Once again, the macular oedema regressed, and visual acuity improved following withdrawal of GH. These ophthalmic changes contra-indicated further GH therapy. CONCLUSION: We suggest that GH may be a risk factor in the development of retinopathy in certain non-diabetic patients, especially in the presence of a severe refractive error.

Child↗
PubMed2006

Incidence and outcomes of mental disorders in a regional population: the Northern Rivers Mental Health Study.

OBJECTIVES: To estimate the incidence of mental disorders in a cohort of previously symptom-free individuals who are representatives of a regional Australian population. To map changing patterns of diagnosis and comorbidity within the cohort over a 2 year period. METHOD: Two year follow-up of a community-based cohort drawn from a telephone screening of 9191 randomly selected adults. Subjects were administered a comprehensive face-to-face interview which included the Composite International Diagnostic Interview. A total of 1407 subjects were interviewed at baseline, and 968 subjects were reinterviewed (a 68.8% follow-up rate). RESULTS: There was considerable change in disorder status over the study period, and analysis of the Composite International Diagnostic Interview scoring suggests that these changes reflected real changes in symptomatology. Of subjects interviewed at both baseline and follow-up, 638 were classified as disorder-free at their entry to the study. After 2 years, 98 of these met criteria for a mental disorder during the preceding 12 months. After adjusting for sampling and gender, the 12 month incidence of any mental disorder among subjects who had been disorder-free 2 years previously was 9.95 per hundred person-years at risk. At baseline, a further 330 subjects met ICD-10 criteria for a mental disorder during the previous 12 months. Two years later, 167 of these subjects (50.6%) were disorder-free, and 163 still met the criteria for a mental disorder, although there had often been considerable change in their diagnosis. Subjects with a mental disorder at the commencement of the study were significantly more likely than those without a disorder to have a positive diagnosis 2 years later (p < 0.001). The number of diagnoses at baseline was a strong predictor of the number of diagnoses at follow-up (p < 0.001), and each additional comorbid diagnosis at baseline also increased the probability of a persisting disorder at follow-up (p < 0.001). CONCLUSIONS: Over a 2 year period, the majority of subjects with a mental disorder will become disorder-free, while a significant number of previously disorder-free individuals will develop a positive diagnosis. Health services need to be designed to meet this labile demand.

Absenteeism↗
PubMed2006

Co-morbid drug and alcohol and mental health issues in a rural New South Wales Area Health Service.

OBJECTIVE: In 2003 the New South Wales (NSW) Centre for Rural and Remote Mental Health (CRRMH) conducted an analysis of co-morbid drug and alcohol (D&A) and mental health issues for service providers and consumers in a rural NSW Area Health Service. This paper will discuss concerns raised by rural service providers and consumers regarding the care of people with co-morbid D&A and mental health disorders. DESIGN: Current literature on co-morbidity was reviewed, and local area clinical data were examined to estimate the prevalence of D&A disorders within the mental health service. Focus groups were held with service providers and consumer support groups regarding strengths and gaps in service provision. SETTING: A rural Area Health Service in NSW. PARTICIPANTS: Rural health and welfare service providers, consumers with co-morbid D&A and mental health disorders. RESULTS: Data for the rural area showed that 43% of inpatient and 20% of ambulatory mental health admissions had problem drinking or drug-taking. Information gathered from the focus groups indicated a reasonable level of awareness of co-morbidity, and change underway to better meet client needs; however, the results indicated a lack of formalised care coordination, unclear treatment pathways, and a lack of specialist care and resources. DISCUSSION: Significant gaps in the provision of appropriate care for people with co-morbid D&A and mental health disorders were identified. Allocation of service responsibly for these clients was unclear. It is recommended that D&A, mental health and primary care services collaborate to address the needs of clients so that a coordinated and systematic approach to co-morbid care can be provided.

Comorbidity↗
PubMed2006

Desire for hastened death in patients with advanced disease and the evidence base of clinical guidelines: a systematic review.

PURPOSE: Patients' desire for hastened death within the context of advanced disease and palliative care is a controversial topic, frequently discussed in the international literature. Much of the discussion has focused on opinion and debate about ethical matters related to hastened death. Not many research studies seem to have specifically targeted why palliative care patients may desire hastened death, and few have focused on clinical guidelines for responding to such requests. METHODS: Using a systematic literature review process, we evaluated the research evidence related to the reasons patients express a desire for a hastened death, and the quality of clinical guidelines in this area. RESULTS: Thirty-five research studies met the inclusion criteria related to reasons associated with a desire for hastened death. The factors associated with a desire to die were often complex and multifactorial; however, psychological, existential and social reasons seem to be more prominent than those directly related to physical symptoms, such as pain. Much of the evidence supporting the reasons for these statements is based on: (a) patients' perceptions of how they may feel in the future, and (b) health professionals' and families' interpretations of why desire to die statements may have been made. Several publications provided expert opinion for responding to requests for physician-assisted suicide and euthanasia. In keeping with this limited research base, there is a lack of evidence-based guidelines for clinical care that addresses the desire to die among terminally ill patients. Most literature has focused on discipline specific responses, with minimal exploration of how clinicians might respond initially to a statement from a patient regarding a desire to die. CONCLUSIONS: In order to advance understanding of the complex issue of desire for hastened death in the context of palliative care, research should focus on studies with patients who have actually made a desire to die statement and the development of guidelines to help health professionals respond. Direction for research in this area is described.

Attitude to Death↗
PubMed2006

Responding to desire to die statements from patients with advanced disease: recommendations for health professionals.

It is not uncommon for patients with advanced incurable disease to express a desire to hasten their death. Health professionals often have difficulty responding to such statements, and find it challenging to ascertain why these statements are made. Health professionals may struggle to determine whether a 'desire to die' statement (DTDS) is about a request for hastened death, a sign of psychosocial distress, or merely a passing comment that is not intended to be heard literally as a death wish. Given the lack of guidelines to assist health professionals with this issue, we have prepared multidisciplinary recommendations for responding to a DTDS, underpinned by key principles of therapeutic communication and a systematic review of empirical literature. Where the relevant literature was lacking, the recommendations were drafted by the authors (clinicians and/ or academics from the following disciplines: nursing, medicine, psychiatry, psychology, sociology, aged care and theology), based on their expert opinion. Multiple drafts of the recommendations were circulated to the authors for refinement until consensus was reached. Strategies for advancing the evidence base for the maturation of guidelines in this area are offered.

Attitude of Health Personnel↗
PubMed2006

Measurement of psychological distress in palliative care.

Research investigating the psychological distress of palliative care patients has contributed to our understanding of the needs and experiences of individuals approaching death. This paper aims to provide a brief review of such measurement of psychological distress in palliative care, focusing on established psychiatric and psychological research tools, and quantitative research methods. This includes clinical screening and diagnostic assessment instruments used to identify key distress-related symptoms and the presence of common clinical syndromes, such as depression, anxiety, delirium, as well as the broader psychological dimensions of suffering, such as existential concerns, spirituality, hope and demoralisation. There are important considerations in undertaking psychological research in palliative care, such as maintaining a balance between the methods and measurements that will address key research questions, and sensitivity to the range of physical and emotional demands facing individuals at the point of receiving palliative care. The clinical application of psychological and psychiatric research tools and methods can aid the detection of psychological distress, aid the thorough assessment of the psychological dimension of the patients' illness and care, aid the identification of individuals who would benefit from specific psychotherapeutic or pharmacologic interventions, and the evaluation of response to treatments.

Anxiety↗
PubMed2006

Actinomycetes (Streptomyces lividans).

Agrobacterium tumefaciens is best known for its ability to transform plants by delivering the T-DNA that is processed and transferred from the resident Ti plasmid to the recipient plant cells. Less well known is the capacity of this Gram-negative bacterium to transfer its T-DNA into fungi and actinomycetes. Procedures are described on the use of the promiscuous T-DNA transfer system of A. tumefaciens to transform members of the actinomycetes. Integration of the T-DNA derivatives into the Streptomyces chromosome provides opportunities of obtaining valuable mutants of this antibiotic producing soil organism.

Actinobacteria↗
PubMed2005

Interface management: effective communication to improve process safety.

Failure to successfully communicate maintenance activities, abnormal conditions, emergency response procedures, process hazards, and hundreds of other items of critical information can lead to disaster, regardless of the thoroughness of the process safety management system. Therefore, a well-functioning process safety program depends on maintaining successful communication interfaces between each involved employee or stakeholder and the many other employees or stakeholders that person must interact with. The authors discuss a process to identify the critical "Interfaces" between the many participants in a process safety management system, and then to establish a protocol for each critical interface.

Chemical Industry↗
PubMed2005

OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha.

Hypoxia-inducible factor 1 (HIF-1) functions as a master regulator of oxygen homeostasis in metazoan species. HIF-1 mediates changes in gene transcription in response to changes in cellular oxygenation. The half-life of the HIF-1alpha subunit is determined by oxygen-dependent prolyl hydroxylation, which is required for binding of the von Hippel-Lindau protein (VHL), the recognition component of an E3 ubiquitin ligase that targets HIF-1alpha for ubiquitination and degradation. Here, we demonstrate that OS-9, the protein product of a widely expressed gene, interacts with both HIF-1alpha and HIF-1alpha prolyl hydroxylases. OS-9 gain-of-function promotes HIF-1alpha hydroxylation, VHL binding, proteasomal degradation of HIF-1alpha, and inhibition of HIF-1-mediated transcription. OS-9 loss-of-function caused by RNA interference increases HIF-1alpha protein levels, HIF-1-mediated transcription, and VEGF mRNA expression under nonhypoxic conditions. These data indicate that OS-9 is an essential component of a multiprotein complex that regulates HIF-1alpha levels in an O2-dependent manner.

Carcinoma, Hepatocellular↗
PubMed2005

Psychosocial impact of newly diagnosed advanced breast cancer.

The purpose of this study was to delineate the key emotional concerns of women newly diagnosed with recurrent or metastatic breast cancer. Sixty-six women diagnosed with metastatic breast cancer within the previous 6 months, receiving treatment at the Medical Oncology Departments of two metropolitan teaching hospitals, completed measures of HADS, IES, CARES-SF and Memorial Symptom Assessment Scale, and participated in a semi-structured interview. There were high levels of psychological morbidity, 56.7% of women younger than 55 years qualifying as "cases" on the HADS, compared with 34.5% of women aged over 55 years. The total HADS score was significantly correlated with the Global and Physical Subscales of the MSAS and CARES. Women younger than 55 years had significantly higher levels of intrusive and avoidant symptoms than women over 55 years. Women also reported high numbers of physical symptoms. Key themes which emerged during the interviews were: difficulties in communicating with doctors, perceived delay in diagnosis, the emotional impact, concerns about the family, feelings about why the cancer developed, other life stress and trauma, and use of non-prescribed treatments.

Adult↗
PubMed2005

Wisdom from the drought: recommendations from a consultative conference.

OBJECTIVE: Drought is a serious and recurring problem for rural and remote Australia. This paper reports the proceedings of a consultative conference concerning the mental health effects of drought held at the Centre for Rural and Remote Mental Health, Orange, in December 2003. The conference objective was to record the collective experience of government and non-government agencies dealing with the effects of drought in rural areas and to collate information for the development of a mental health strategy for future drought. DESIGN: Participants were recruited in consultation with rural mental health organisations. Questions about mental health service strategies to minimise and respond to the mental health impact of the drought were posed to participants. Qualitative data were collected using a Nominal Group Technique. SETTING: The Centre for Rural and Remote Mental Health, Bloomfield Hospital, Orange, New South Wales. PARTICIPANTS: Twenty-three professionals participated, including representatives from New South Wales Health, Mental Health, and Agriculture; the Department of Community Services, and Rural Financial Counsellors. MAIN OUTCOME MEASURE: Qualitative analysis of participant responses. RESULTS: Three general strategies emerged as the most beneficial in minimising adverse mental health outcomes in times of drought: community-building and education about the physical, financial and mental health effects of drought; co-operation between and co-ordination of agencies in delivering mental health and other drought support; and continuity and planning of improved mental health services. CONCLUSIONS: Drought has a serious effect on the mental health of communities. It is important to plan a response beyond the end of the drought, bringing together different government and non-government agencies to build community capacity to address common mental health needs.

Congresses as Topic↗
PubMed2003

Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1.

Prostaglandin E(2) (PGE(2)) has been implicated as an inducer of angiogenesis in human colon cancer. Here, we demonstrate that PGE(2) exposure induces the expression of vascular endothelial growth factor (VEGF) mRNA in HCT116 human colon carcinoma cells that is mediated by the transcriptional activator hypoxia-inducible factor 1 (HIF-1). PGE(2) exposure induces the phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. Pharmacologic inhibition of ERK phosphorylation blocks the induction of VEGF mRNA and HIF-1alpha protein expression in response to PGE(2) stimulation. Inhibition of C-SRC tyrosine kinase activity also blocks PGE(2)-induced HIF-1alpha protein and VEGF mRNA expression without blocking ERK phosphorylation. In contrast, phosphorylation of AKT is dependent on ERK and C-SRC activity. Thus, the activity of multiple signal transduction pathways is required for the HIF-1-mediated induction of VEGF expression in colon cancer cells exposed to PGE(2).

CSK Tyrosine-Protein Kinase↗
PubMed2003

Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1.

Hypoxia-inducible factor 1 (HIF-1) transactivates genes the products of which mediate tumor angiogenesis and glycolytic metabolism. Overexpression of the HIF-1 alpha subunit, resulting from intratumoral hypoxia and genetic alterations, has been demonstrated in common human cancers and is correlated with tumor angiogenesis and patient mortality. Here we demonstrate that hypoxia or HIF-1 alpha overexpression stimulates Matrigel invasion by HCT116 human colon carcinoma cells, whereas this process is inhibited by a small interfering RNA directed against HIF-1 alpha. We show that HIF-1 regulates the expression of genes encoding cathepsin D; matrix metalloproteinase 2; urokinase plasminogen activator receptor (uPAR); fibronectin 1; keratins 14, 18, and 19; vimentin; transforming growth factor alpha; and autocrine motility factor, which are proteins that play established roles in the pathophysiology of invasion. Neutralizing antibodies against uPAR block tumor cell invasion induced by hypoxia or HIF-1 alpha overexpression. These results provide a molecular basis for promotion of the invasive cancer phenotype by hypoxia and/or HIF-1 alpha overexpression.

Animals↗
PubMed2003

Doctors and their patients: a context for understanding the wish to hasten death.

There is a paucity of research that has directly examined the role of the health professional in dealing with a terminally ill patient's wish to hasten death (WTHD) and the implications of this for the support and services needed in the care for a dying patient. Themes to emerge from a qualitative analysis of interviews conducted on doctors (n=24) involved in the treatment and care of terminally ill patients were (i). the doctors' experiences in caring for their patients (including themes of emotional demands/expectations, the duration of illness, and the availability of palliative care services); (ii). the doctors' perception of the care provided to their respective patients (comprising themes concerning satisfaction with the care for physical symptoms, for emotional symptoms, or overall care); (iii). the doctors' attitudes to euthanasia and (iv). the doctors' perception of their patients' views/beliefs regarding euthanasia and hastened death. When responses were categorised according to the patients' level of a WTHD, the theme concerning the prolonged nature of the patients' illnesses was prominent in the doctor group who had patients with the highest WTHD, whereas there was only a minority of responses concerning support from palliative care services and satisfaction with the level of emotional care in this group.This exploratory study presents a set of descriptive findings identifying themes among a small group of doctors who have been involved in the care of terminally ill cancer patients, to investigate factors that may be associated with the WTHD among these patients. The pattern of findings suggest that research investigating the doctor-patient interaction in this setting may add to our understanding of the problems (for patients and their doctors) that underpins the wish to hasten death in the terminally ill.

Adult↗
PubMed2002

Germline sequence variants of the LZTS1 gene are associated with prostate cancer risk.

The 8p22 through p23 region has been identified as a potential site for genes associated with prostate cancer. The gene LZTS1 has been mapped to the 8p22 through p23 region and identified as a potential tumor suppressor based on loss of heterozygosity studies using primary esophageal tumors. Sequence analysis of mRNA from various tumors has revealed multiple mutations and aberrant mRNA transcripts. The most recent report associates LZTS1 function with stabilization of p34(cdc2) during the late S-G2/M stage of mitosis, affecting normal cell growth. In this study, a detailed DNA sequence analysis of LZTS1 was performed in a screening panel consisting of sporadic and hereditary prostate cancer (HPC) cases and unaffected controls. Twenty-four SNP, 15 of which were novel, were identified in germline DNA. Four coding SNP were identified. Eleven informative SNP were genotyped in 159 HPC probands, 245 sporadic prostate cancer cases, and 222 unaffected controls. Four of these SNP were statistically significant for association with prostate cancer (P < or = 0.04). These results add evidence supporting a role of LZTS1 in prostate cancer risk.

Base Sequence↗
PubMedDate not supplied

Risk factors for development of delirium among oncology patients.

To determine the occurrence of delirium in oncology inpatients and to identify and evaluate admission characteristics associated with the development of delirium during inpatient admission, a prospective observational study was conducted of 113 patients with a total of 145 admissions with histological diagnosis of cancer admitted to the oncology unit over a period of ten weeks. At the point of inpatient admission, all patients were assessed for the presence of potential risk factors for development of delirium. During the index admission patients were assessed daily for the presence of delirium using the Confusion Assessment Method. Delirium was confirmed by clinician assessment. Delirium developed in 26 of 145 admissions (18%) and 32 episodes of delirium were recorded with 6 patients having 2 episodes of delirium during the index admission. Delirium occurred on average 3.3 days into the admission. The average duration of an episode of delirium was 2.1 day. Four patients with delirium (15%) died. All other cases of delirium were reversed. Factors significantly associated with development of delirium on multivariate analysis were: advanced age, cognitive impairment, low albumin level, bone metastases, and the presence of hematological malignancy. Hospital inpatient admission was significantly longer in delirium group (mean: 8.8 days vs 4.5 days in nondelirium group, P<.01). Delirium among hospitalized oncology patients is a common condition. Identification of risk factors to delirium at the time of inpatient admission can be used to recognize those patients at the greatest risk and may aid prevention, early detection and treatment.

Age Factors↗
PubMedDate not supplied

Association between apolipoprotein E epsilon4 and neuropsychiatric symptoms during interferon alpha treatment for chronic hepatitis C.

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Adult↗