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Biomedical subjects

M Kennedy

Publications and source records attributed to M Kennedy.

At least 19 recordsLinked to original sources

Genetic relatedness and pathogenicity of equine herpesvirus 1 isolated from onager, zebra and gazelle.

Equine herpesvirus 1 was isolated from an onager in 1985, a zebra in 1986 and a Thomson's gazelle in 1996 in USA. The genetic relatedness and pathogenicity of these three viruses were investigated based on the nucleotide sequences of the glycoprotein G (gG) gene, experimental infection in hamsters, and comparison with horse isolates. The gG gene sequences of EHV-1 from onager and zebra were identical. The gG gene sequences of the gazelle isolate showed 99.5% identity to those of onager and zebra isolates. The gG gene sequences of EHV-1 isolated from horses were 99.9-100% identical and 98, 98 and 97.8% similar to gG from onager, zebra and gazelle isolates, respectively. Hamsters inoculated with onager, zebra and gazelle isolates had severe weight loss, compared with hamsters inoculated with horse isolates. The histopathological findings were related to the virulence of each isolate. The results indicated that EHV-1 isolates from onager, zebra and gazelle differ from horse EHV-1 and are much more virulent in hamsters.

Amino Acid Sequence↗

Molecular characterisation of pneumococcal serotype 16F: Established predominant carriage and otitis media serotype in the 7vPCV era.

Young Australian Aboriginal children in remote communities experience very high rates of pneumococcal carriage and otitis media. Prior to introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV, Prevenar), serotype 16F was an important type found in nasal and ear discharge swabs. Since commencement of pneumococcal immunisation for Aboriginal infants in 2001, 16F has become the predominant established serotype in carriage and otitis media in young Aboriginal children. BOX typing and multi-locus sequence typing revealed a diverse population of serotype 16F strains, and evidence of potential capsule switching from a vaccine serotype 4 to a serotype 16F.

Australia↗

Efficacy of repeated high-dose hepatitis B vaccine (80 microg) in patients with chronic liver disease.

Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B (HBV) vaccine given as sequential 20 microg IM shots because of an overall impaired immune response. Many of these patients go on to liver transplantation and are at risk of acquiring recurrent or de novo HBV infection. To evaluate the efficacy and safety of high-dose (80 microg) IM HBV vaccination in patients with CLD who had previously failed to respond to a standard three-dose schedule of 40 microg IM vaccine given monthly. A retrospective review was undertaken at our institution of 79 patients with CLD who were treated with high-dose (80 microg) HBV vaccinations. All had previously failed a three-dose course of 40 microg HBV vaccine. An HBV vaccine response was defined as an anti-HBs titer greater than 100 mIU/ml. Liver enzymes, creatinine, age, prothrombin time, total vaccine dose, and MELD score were recorded. No adverse events were reported. Seventy-two per cent (57/79) of the subjects had an adequate response after receiving a mean total dose of 220 mug vaccine (range 80-800 microg). Twenty-eight per cent (22/79) of the subjects did not respond after receiving a mean total dose of 420 microg vaccine (range 240-720 microg). Non-responders had more severe hepatic disease defined as a higher mean total bilirubin level (p = 0.003) and a lower mean albumin level (p < 0.05). Age, prothrombin time, MELD score, and creatinine were not statistically significant between the responders and non-responders. Repeated high-dose (80 microg) HBV vaccination, in patients who do not respond to standard HBV vaccine doses, is safe and effective in the majority of patients with CLD.

Adult↗

Estrogen receptor alpha and beta profiling in human breast cancer.

BACKGROUND: The identification of a second estrogen receptor (ER-beta) has significant implications for therapeutic strategy in breast cancer management arising from the potential agonist effect of Tamoxifen at estrogen receptor sites and as such, antiestrogen therapy may be inappropriate in patients with a dominance of ER-beta. METHODS: To determine the proportion of breast cancer patients who may be so at risk, we developed a novel multiplexed RT-PCR technique to establish the relative ER-alpha and ER-beta levels in 53 primary breast cancers, 11 normal breast tissues and six cell lines. We further assessed the prognostic significance of receptor status relative to the Nottingham prognostic index (NPI). The ER-alpha and ER-beta status was also determined by immunohistochemistry using previously published and 'in-house' scoring systems. RESULTS: Using RT-PCR analysis, 46 tumours were hormone receptor positive (ER+) with 42 displaying ER-alpha predominance. Comparison with immunohistochemistry demonstrated 44/53 (ER-alpha) and 27/50 (ER-beta) concordance rates. There was no significant difference in the NPI between ER-alpha and ER-beta predominant cohorts or between ER+ and ER- cohorts. CONCLUSION: This study identifies the existence of a subgroup of ER+ patients in whom Tamoxifen therapy may be inappropriate and has significant implications for adjuvant therapy of primary breast cancer.

Adult↗

The potential signalling pathways which regulate surface changes induced by phytohormones in the potato cyst nematode (Globodera rostochiensis).

It has been demonstrated that the surface lipophilicity of the plant-parasitic nematode Globodera rostochiensis decreases when infective larvae are exposed to the phytohormones indole-3-acetic acid (auxin) or kinetin (cytokinin). In the present study, it was shown that inhibition of phospholipase C (PLC) or phosphatidylinositol 3 kinase (PI3-kinase) reversed the effect of phytohormones on surface lipophilicity. The signalling pathway(s) involved in surface modification were investigated using 'caged' signalling molecules and stimulators or inhibitors of different signalling enzymes. Photolysis of the 'caged' signalling molecules, NPE-caged Ins 1,4,5-P3, NITR-5/AM or caged-cAMP to liberate IP3, Ca2+ or cAMP respectively, decreased the surface lipophilicity. Activation of adenylate cyclase also decreased the surface lipophilicity. In contrast, inhibition of PI3-kinase using Wortmannin, LY-294002 or Quercetin, and inhibition of PLC using U-73122 all increased the surface lipophilicity. Two possible signalling pathways involved in phytohormone-induced surface modification are proposed.

Adenine↗

Pathology and clinical relevance of radial scars: a review.

Radial scar (RS) is a benign, well recognised, radiological and pathological entity. Histologically, it is characterised by a fibroelastotic core with entrapped ducts and surrounding radiating ducts and lobules. Postmortem studies indicate that these lesions are present commonly in the population, especially in association with benign breast disease. In recent years, their clinical relevance has assumed more importance with the introduction of population based screening programmes. The exact pathogenesis of RS is unknown. Accumulating evidence indicates that they are associated with atypia and/or malignancy and, in addition, may be an independent risk factor for the development of carcinoma in either breast. In view of the association with atypia and malignancy, excision biopsy is justified in RS, although it has been argued that core biopsy evaluation and surveillance may be appropriate in selected patients.

Biopsy↗

Effects of phytohormones on the surfaces of plant-parasitic nematodes.

The direct effects of phytohormones (auxin and kinetin) and root diffusates on the surface lipophilicity of the plant parasitic nematodes Globodera rostochiensis and Meloidogyne incognita were investigated. The fluorescent lipid probe AF18 (5-N(octodecanoyl) aminofluorescein) was used to detect surface changes. Root diffusates increased AF18 uptake by G. rostochiensis while it had no effect on M. incognita. Kinetin and auxin decreased AF18 uptake in G. rostochiensis, while they had the opposite effect on M. incognita. Auxin/kinetin ratio was also found to be important in triggering the surface changes, especially at high concentrations. Whether plant nematodes have auxin and/or kinetin binding proteins is discussed as well as the mechanism behind the surface lipophilicity changes due to root diffusates and phytohormones.

Adenine↗

Deletions in the 7a ORF of feline coronavirus associated with an epidemic of feline infectious peritonitis.

A population of Persian cats experienced an epidemic of feline infectious peritonitis (FIP) over 2 years. Twelve cases of FIP occurred in litters born during this period. Cats contracting FIP were all genetically related through the sire. Feline coronavirus (FCoV) genomic RNA was detected consistently in this study in biologic samples from adult cats, kittens suffering from FIP, and their siblings. Analysis of viral 7a/7b open reading frame (ORFs) were analyzed and revealed two distinct virus variants circulating in the population, one with an intact 7a ORF and one with two major deletions in the 7a ORF. The 7b ORFs were intact and similar among all virus isolates, although point mutations resulting in amino acid changes were present. The sire was determined to be infected with both variants, and was persistently virus-infected. We speculate the deletion variant arose from the non-deletion variant during viral replication in this population, possibly in the sire.

Amino Acid Sequence↗

Health and risk behaviors over time among youth living with HIV.

Health practices and transmission behaviors were examined over time among 25 disabled youth living with HIV (YLH) living in a comprehensive residential care program. YLH were aged 19-24 years (M=23.4 years); 89 per cent of males were gay, bisexual, or transgendered (60% Caucasian); all had physical and mental health problems, as well as substance abuse disorders. YLH were assessed at least four times at 3-month intervals and reported high lifetime rates of sexual and substance-use risk acts. Over four assessments, YLH improved their nutrition and hygiene and decreased their worry about their health status. YLH evidenced no decrease in the frequency of substance use and sexual risk. Depression, self-esteem, and health status also were stable over time. YLH who have a lifetime history of multiple problem behaviors are likely to change slowly over time, even when receiving comprehensive residential care.

Adolescent↗

Identification and functional expression in yeast of a prenylcysteine alpha-carboxyl methyltransferase gene from Arabidopsis thaliana.

Most isoprenylated proteins are alpha-carboxyl-methylated. However, despite numerous studies linking protein isoprenylation in plants to cell cycle control, meristem development, and phytohormone signaling, alpha-carboxyl methylation of isoprenylated plant proteins has not been characterized in detail. Here, we report the cloning of a prenylcysteine alpha-carboxyl methyltransferase gene (AtSTE14) from Arabidopsis thaliana. AtSTE14 restores fertility and enzymatic activity to a ste14 mutant of Saccharomyces cerevisiae, confirming its identity as a bona fide prenylcysteine alpha-carboxyl methyltransferase gene. Furthermore, the presence of AtSTE14 transcripts in various Arabidopsis organs suggests a ubiquitous role for the AtSTE14 protein in plant growth and development. These results demonstrate that Arabidopsis thaliana possesses a functional prenylcysteine alpha-carboxyl methyltransferase involved in post-isoprenylation protein processing.

Amino Acid Sequence↗

Quality management and the Emergency Services Enhancement Program.

Since the introduction of the Emergency Services Enhancement Program (ESEP) in Victoria in 1995, improvements have been demonstrated in the indicators relating to Emergency waiting times, ambulance bypass rates and inpatient bed access block. This study focuses on staff perceptions of changes in these indicators, factors perceived to influence performance improvements and the extent to which ESEP is perceived to have contributed to overall patient care. A questionnaire was directed at four focus groups within each of the hospitals participating in ESEP. These were Chief Executive Officers, Emergency Department Directors and Nurse Unit Managers, bed coordinators and personnel from the Emergency Department floor. A total of 101 staff responded. Emergency Department staff were generally accurate in their perceptions of performance changes. The most important factors effecting the changes were perceived to be changes in staff profile, management of patient flow through the department, changes in administrative policies and changes in work practices. Staff perceived that patient care has improved by 10% since 1995 and that ESEP has contributed 8% of this improvement. Staff have perceived improvements in ESEP performance indicators consistent with actual changes. The possible mechanisms by which these changes have occurred are presented and discussed. Factor analysis indicated that changes perceived to be most likely to result in improvements were: changes in staff profile (seniority), managing the flow of patients through emergency departments, changing administrative policies, changes in work practices and changes in staff numbers. Improvements in patient care were considered partly due to ESEP. In addition, ESEP has raised awareness of quality management issues.

Attitude of Health Personnel↗

Anesthetic efficacy of ropivacaine in maxillary anterior infiltration.

OBJECTIVE: The purpose of this prospective, randomized double-blind study was to evaluate and compare the anesthetic efficacy of 0.5% ropivacaine with 1:200,000 epinephrine, of 0.5% ropivacaine, and of 0.5% bupivacaine with 1:200,000 epinephrine in maxillary lateral incisor infiltrations. STUDY DESIGN: Forty subjects randomly received, in a double-blind manner, 3 infiltrations at 3 separate appointments, in a repeated-measures design. The injections consisted of an infiltration of 1.8 mL of 0.5% ropivacaine plain, an infiltration of 1.8 mL of 0.5% ropivacaine with 1:200,000 epinephrine, and an infiltration of 1.8 mL of 0.5% bupivacaine with 1:200,000 epinephrine (control solution). The maxillary lateral incisor pulpal anesthesia was evaluated with an electric pulp tester at 2-minute cycles for 90 minutes after injection. No response from the subject to the maximum output (80 reading) of the pulp tester was used as the criterion for pulpal anesthesia. Anesthesia was considered successful when 2 consecutive 80 readings were obtained. The duration of pulpal anesthesia was recorded as the last 80 reading. RESULTS: One hundred percent of the subjects had lip numbness with all solutions. The anesthetic success rates for ropivacaine plain, ropivacaine with epinephrine, and bupivacaine with epinephrine were 68%, 75%, and 80%, respectively. There were no significant differences (P >.05) among the solutions. The duration of pulpal anesthesia (80 readings) for ropivacaine plain, ropivacaine with epinephrine, and bupivacaine with epinephrine was 13 minutes, 33 minutes, and 33 minutes, respectively. Ropivacaine plain had a significantly shorter duration of pulpal anesthesia than ropivacaine with epinephrine. CONCLUSIONS: We concluded that 0.5% ropivacaine with 1:200,000 epinephrine was equivalent to 0.5% bupivacaine with 1:200,000 epinephrine in pharmacologic action. The duration of pulpal anesthesia was less for ropivacaine without epinephrine. Ropivacaine with epinephrine has the potential to replace bupivacaine with epinephrine in clinical dental practice because of the decreased potential for cardiac and central nervous system toxicity.

Adult↗

Health promotion-who, us? Developing health promoting emergency departments.

This paper describes the initiation of Victoria's Health Promoting Emergency Departments (HPEDs) Program, involving seven of Melbourne's Emergency Departments (EDs). The Program aims to integrate health promotion into the function of EDs, to complement the clinical and curative emergency care that they already provide. A development phase identified the means of achieving this and involved establishing a multi-disciplinary Steering Committee and engaging health promotion specialists to record the opportunities for health promotion within the ED context. A literature review, and consultations with ED staff (focus groups and surveys) and other stakeholders were conducted. A concept paper was published and the development phase findings were documented, including recommendations on the future of the Program.

Emergency Service, Hospital↗

Survey of intensive care units and availability of drug assays in Australasia.

The availability of drug assays, toxicologic screens, or both can play a significant role in the clinical decision-making processes affecting comatose patients with brain injury, including the decision to continue life support. However, with the widespread trend to reduce such comprehensive laboratory services down to core routine drugs, many clinical staff are finding it increasingly difficult to obtain such assay results in a time-frame relevant to the clinical needs of their patients and families. The authors have surveyed the intensive care units in Australasia to assess their perspectives in this area. The results from 53% of units responding showed there was insufficient clinical pharmacologic support available. Whereas the majority of centers had ready access to the standard immunoassays and urine drug screens, few had access to more complex assays, especially in the time-frame that was required. Interestingly, there was wide variability between centers as to the time to terminate life support in the absence of other indices (e.g., 4-vessel angiography). The use of basic pharmacokinetic principles including drug half-life was practiced in some centers, albeit probably inappropriately in this patient subpopulation. There is generally insufficient availability of specialized drug assay laboratories to meet clinical demands, primarily because of reduction in services and financial constraints in the public hospital system.

Australia↗

Successful and sustained treatment of chronic radiation proctitis with antioxidant vitamins E and C.

OBJECTIVE: Chronic radiation proctitis, a common sequelae of pelvic radiation, is characterized by obliteration of the submucosal vasculature with subsequent ischemia and reperfusion injury. Oxidative stress is thought to be a major mechanism in radiation proctitis. Therefore, antioxidants (vitamins E and C) may be beneficial. METHODS: Twenty consecutive symptomatic outpatients with endoscopically documented radiation proctitis seen in a single gastroenterology clinic were given a combination of vitamin E (400 IU tid) and vitamin C (500 mg tid). Previous radiation therapy was given for prostatic (n = 10) or gynecological (n = 10) malignancies. These patients presented with one or more of the following symptoms: rectal bleeding, rectal pain, diarrhea, or fecal urgency. Using a questionnaire, these symptoms were rated by the patients in terms of their severity (grade 0-4) and frequency (grade 0-4) before and after treatment with vitamins E and C. A symptom index was calculated by the addition of the severity and frequency scores (8 = most symptomatic). The lifestyle impact of the symptoms was also assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home). Among these 20 patients, 10 patients who received vitamins E and C for 1 yr were assessed again to determine whether their initial responses were sustained. RESULTS: There was a significant (p < 0.05; Wilcoxon rank) improvement in the symptom index (before treatment vs after treatment with vitamins E and C) for bleeding (median score: 4 vs 0), diarrhea (median score: 5 vs 0), and urgency (median score: 6 vs 3). Patients with rectal pain did not improve significantly. Bleeding resolved in four of 11 patients, diarrhea resolved in eight of 16 patients, fecal urgency resolved in three of 16 patients, and rectal pain resolved in two of six patients. Lifestyle improved in 13 patients, including seven patients who reported a return to normal. Two of the patients with no improvement in their daily symptoms also had radiation ileitis. All 10 patients who underwent a second follow-up interview reported sustained improvement in their symptoms 1 yr later. CONCLUSION: A substantial number of patients with radiation proctitis seem to benefit from antioxidant therapy. A double-blind placebo-controlled trial is needed to confirm this open-labeled pilot study.

Aged↗