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Biomedical subjects

M Robertson

Publications and source records attributed to M Robertson.

At least 19 recordsLinked to original sources

A case of hydatid cyst associated with postpartum maternal death.

A young, apparently healthy woman from a rural area in South Africa presented in the third trimester of pregnancy with a symptomatic abdominal mass between the uterine fundus and liver. The etiology was established to be an echinococcus cyst of the liver and medical treatment was initiated. The fetal outcome was good but the mother died 3 days postpartum due to an unusual but devastating complication of the hydatid cyst.

Adolescent↗

Providing guidelines and education is not enough: an audit of gentamicin use at The Royal Melbourne Hospital.

BACKGROUND: Aminoglycoside antibiotics are commonly prescribed for the treatment of Gram-negative infections. Appropriate dosing and therapeutic monitoring of aminoglycosides are important because these agents have a narrow therapeutic index. AIM: To audit gentamicin use at our hospital, focusing on selection of the initial dose and therapeutic monitoring practices, and to compare the results against recommendations in the existing hospital aminoglycoside guidelines, which had recently been promoted to doctors. METHODS: This audit included all inpatients receiving gentamicin at The Royal Melbourne Hospital from 1 February to 12 March 2004. The principal researcher checked the drug charts of all inpatients to identify those receiving gentamicin and collected data from the medical records and the pathology database. Doses were considered 'concordant' if the dose given was within the recommended dosing range +/-20 mg. RESULTS: A total of 132 courses of gentamicin was included in the study. Gentamicin was prescribed for prophylaxis in 31.1% of courses. Thirty-six per cent of patients prescribed gentamicin were more than 65 years of age. Eighty-two per cent of the gentamicin used therapeutically was given as a single daily dose. Sixty-six per cent of gentamicin initial dosing was not in accordance with existing hospital guidelines. Seventy-seven per cent of gentamicin courses requiring therapeutic drug monitoring received such monitoring; however, in only 8.8% of these was the monitoring conducted according to guidelines. CONCLUSION: Aminoglycoside prescribing practices at our hospital are suboptimal, despite ready access to prescribing guidelines. Provision of a guideline and education sessions with doctors do not necessarily lead to widespread adoption of recommended practices. We suggest that changes to hospital systems related to prescribing and monitoring of aminoglycosides are required.

Aged↗

Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate.

OBJECTIVE: This study aimed to determine the extent of agreement between central venous and arterial values for pH, bicarbonate, base excess, and lactate in a group of intensive care unit (ICU) patients. METHODS: A prospective study of a convenience sample of patients deemed by their treating doctor to require blood gas analysis as part of their clinical care in ICU. It compared pH, bicarbonate, base excess and lactate on arterial and central venous samples taken within five minutes of each other. Data were analysed using bias (Bland-Altman) methods. RESULTS: A total of 168 matched sample pairs from 110 patients were entered into the study. All variables showed close agreement. The mean difference between arterial and venous values of pH was 0.03 pH units, for bicarbonate 0.52 mmol/l, for lactate 0.08 mmol/l, and for base excess 0.19 mmol/l. All showed acceptably narrow 95% limits of agreement. CONCLUSION: Central venous pH, bicarbonate, base excess, and lactate values showed a high level of agreement with the respective arterial values, with narrow 95% limits of agreement. These results suggest that venous values may be an acceptable substitute for arterial measurement in this clinical setting.

Acid-Base Imbalance↗

Group interpersonal psychotherapy for postnatal depression: a pilot study.

We conducted a pilot study to assess the potential effectiveness of group interpersonal psychotherapy (IPT-G) as a treatment for postnatal depression (PND). The study was also established to test a treatment manual for IPT-G, assess the acceptability of this format for participants and test a recruitment strategy for a randomised controlled trial. 18 mothers diagnosed with PND participated in 2 individual session and 8 sessions of group IPT. A two-hour psychoeducational session was also held for the partners of the participants. Measures of depressive symptomatology and social adjustment were administered by an independent clinician at baseline, 4 weeks, 8 weeks and 3 months post treatment. Patient satisfaction with the treatment was also evaluated. Severity scores on the BDI, EPDS and the HDRS decreased from pre- to post-treatment. This was maintained at three months follow up. No overall improvement in the Social Adjustment Scale-Self Report was noted, although there was improvement in their relationship with their significant other. The results confirm previous work that IPT-G may improve symptom severity for women suffering from postnatal depression. Limitations included the use of antidepressant therapy by 67% of subjects and the lack of a control group. There is a need for further randomised controlled trials of IPT-G with larger sample sizes to establish its effectiveness as treatment for PND.

Adult↗

Clinical features and associated psychopathology in a Tourette syndrome cohort.

OBJECTIVE: This study explored in detail the association between tic symptomatology, related clinical variables, and psychopathology in 91 consecutive adult TS subjects from a UK clinic. METHODS: Consecutive patients from a specialized Tourette clinic who met the DSM-III criteria for TS were evaluated using standardized rating scales for Tourette syndrome and other psychopathology. RESULTS: The male female ratio in our cohort was 1.8:1. Significantly more males had an earlier age at onset of TS and history of birth complications. Obsessive compulsive behaviors in the patient was positively correlated with presence of attention deficit hyperactivity disorder and self-injurious behaviors. With regard to adult psychopathology, principal components factor analysis yielded two factors, 'obsessionality' and 'anxiety/depression', which accounted for 72% of the variance. CONCLUSION: Our results support the high occurrence of anxiety, depression and obsessionality in adult TS subjects.

Adolescent↗

A randomized study (WOS MM1) comparing the oral regime Z-Dex (idarubicin and dexamethasone) with vincristine, adriamycin and dexamethasone as induction therapy for newly diagnosed patients with multiple myeloma.

Whilst infusional vincristine, adriamycin and dexamethasone (VAD) is an effective treatment for patients with multiple myeloma (MM), administration may be complicated by line-associated infections and thromboses. The oral regime, Z-Dex (idarubicin and dexamethasone) has been shown to be efficacious in MM. We conducted a randomized study comparing Z-Dex with VAD as induction therapy in newly diagnosed MM patients. A total of 106 patients (median age, 56 years; range: 37-73; Durie-Salmon stage II/III) were randomized to receive four to six cycles of Z-Dex or VAD. Central line complications were reported in 38 patients on 57 cycles, primarily because of infection. Neutropenia (all grades) was more common in the Z-Dex arm (P = 0.009) although grade III/IV neutropenia was not significantly different between the treatment groups (P = 0.06). Infections (all grades) were more commonly seen in the VAD arm (P = 0.001) although grade III/IV infections were not significantly different between the two groups (P = 0.081). The responses to therapy (complete/partial response) in evaluable patients were: VAD 74% vs. Z-Dex 58%, with an estimated difference in response of 16% (95% CI -2-33, P = 0.075). VAD recipients (15%) suffered early treatment-related mortality compared with 12% of Z-Dex recipients. Overall, 45 patients have died: disease progression (Z-Dex n = 13, VAD n = 10), regimen-related toxicity (Z-Dex n = 2, VAD n = 2), infection (Z-Dex n = 0, VAD n = 3), other causes (Z-Dex n = 7, VAD n = 2), unknown (Z-Dex n = 3, VAD n = 2). This study demonstrated that Z-Dex might be a suitable oral alternative to VAD for treating newly diagnosed MM patients, although definitive evidence for equivalence is not provided.

Adult↗

Novel P2X7 receptor antagonists.

The synthesis and pharmacological evaluation of a new series of potent P2X(7) receptor antagonists is disclosed. The compounds inhibit BzATP-mediated pore formation in THP-1 cells. The distribution of the P2X(7) receptor in inflammatory cells, most notably the macrophage, mast cell and lymphocyte, suggests that P2X(7) antagonists have a significant role to play in the treatment of inflammatory disease.

Adenosine Triphosphate↗

Prenatal diagnosis of congenital leukemia in a fetus at 25 weeks' gestation with Down syndrome: case report and review of the literature.

Leukemia in a hydropic fetus with hepatosplenomegaly and Down syndrome was diagnosed at 25 weeks' gestation. Spontaneous demise occurred 10 days after the cordocentesis. A review of the literature of the seven cases described antenatally and 10 cases described in the immediate neonatal period or on examination of the stillborn baby is presented.

Adult↗

Factors associated with the wish to hasten death: a study of patients with terminal illness.

BACKGROUND: There is considerable debate regarding the clinical issues surrounding the wish to hasten death (WTHD) in the terminally ill. The clinical factors contributing to the WTHD need further investigation among the terminally ill in order to enhance understanding of the clinical assessment and treatment needs that underlie this problem. A more detailed understanding may assist with the development of appropriate therapeutic interventions. METHOD: A sample of terminally ill cancer patients (N = 256) recruited from an in-patient hospice unit, home palliative care service and a general hospital palliative care consulting service from Brisbane Australia between 1998-2001 completed a questionnaire assessing psychological (depression and anxiety), social (family relationship, social support, level of burden on others) and the impact of physical symptoms. The association between these factors and the WTHD was investigated. RESULTS: A high WTHD was reported by 14 % of patients. A discriminant function analysis revealed that the following variables were associated with a high WTHD (P < 0.001): higher levels of depressive symptoms, being admitted to an in-patient hospice setting, a greater perception of being a burden on others, lower family cohesion, lower levels of social support, higher levels of anxiety and greater impact of physical symptoms. CONCLUSIONS: Psychological and social factors are related to a WTHD among terminally ill cancer patients. Greater attention needs to be paid to the assessment of psychological and social issues in order to provide appropriate therapeutic interventions for terminally ill patients.

Adult↗

High glucose concentration decreases insulin-like growth factor type 1-mediated mitogen-activated protein kinase activation in bovine retinal endothelial cells.

Clinical trials have incontrovertibly demonstrated that the onset and progression of diabetic retinopathy (DR) is influenced by the control of glucose levels in patients. In the present study, we examined the effect of glucose concentration on the responsiveness of bovine retinal endothelial cells (BREC) to insulin-like growth factor type 1 (IGF-1). Retinal endothelial cells were isolated from bovine retina and cultured in 5 or 20 mmol/L glucose with or without 100 ng/mL IGF-1. The level of cell growth and p42/44 and p38 mitogen-activated protein kinase (MAPK) activation was determined using the alamarBlue (Serotech) assay and Western blotting, respectively. IGF-1 significantly enhanced cell growth in BREC exposed to 5 mmol/L glucose but not in cells exposed to high glucose concentrations (20 mmol/L). IGF-1 induced a transient activation of p42/44 MAPK, with peak activation at 15 minutes in cells exposed to 5 mmol/L glucose; however, no increase in p42/44 MAPK was evident at the higher glucose concentration of 20 mmol/L. There was no significant change in the level of p38 MAPK during the time period examined when IGF-1 was also present. However, high glucose concentrations alone increased the level of p38 MAPK after 60 minutes and the level of p42/44 MAPK after only 15 minutes exposure in 20 mmol/L glucose. Thus, BREC exposed to high glucose concentrations are not sensitive to IGF-1 and this is due, at least in part, to a reduced activation of the p42/44 MAPK pathway. Furthermore, the presence of IGF-1 appears to exert a protective effect on the cells in high glucose concentration by preventing progression through the cell cycle.

Animals↗

High resolution computed tomographic assessment of airway wall thickness in chronic asthma: reproducibility and relationship with lung function and severity.

BACKGROUND: In some patients chronic asthma results in irreversible airflow obstruction. High resolution computed tomography (HRCT) has been advocated for assessing the structural changes in the asthmatic lung and permits investigation of the relationships between airway wall thickening and clinical parameters in this condition. METHODS: High resolution CT scanning was performed in 49 optimally controlled asthmatic patients and measurements of total airway and lumen diameter were made by two independent radiologists using electronic callipers. Wall area as % total airway cross sectional area (WA%) and wall thickness to airway diameter ratio (T/D) were calculated for all airways clearly visualised with a transverse diameter of more than 1.5 mm, with a mean value derived for each patient. Intra- and inter-observer variability was assessed for scope of agreement in a subgroup of patients. Measurements were related to optimum forced expiratory volume in 1 second (FEV1), forced mid expiratory flow, carbon monoxide gas transfer, two scores of asthma severity, airway inflammation as assessed with induced sputum, and exhaled nitric oxide. RESULTS: Neither observer produced a statistically significant difference between measurements performed on two occasions but there was a significant difference between observers (limits of agreement -2.6 to 6.8 for WA%, p<0.0001). However, mean WA% measured on two occasions differed by no more than 5.4% (limits of agreement -4.0 to 5.4; mean (SD) 0.7 (2.4)). Statistically significant positive associations were observed between both WA% and T/D ratio and asthma severity (r(S)=0.29 and 0.30, respectively, for ATS score), and an inverse association with gas transfer coefficient was observed (r(S)=-0.43 for WA% and r(S)=-0.41 for T/D). No association was identified with FEV1 or airway inflammation. CONCLUSIONS: The airway wall is thickened in more severe asthma and is associated with gas transfer coefficient. This thickening does not relate directly to irreversible airflow obstruction as measured with FEV1.

Airway Obstruction↗

Terminally ill cancer patients' wish to hasten death.

This exploratory study investigated factors associated with the wish to hasten death among a sample of terminally ill cancer patients. Semi-structured interviews conducted on a total of 72 hospice and home palliative care patients were subjected to qualitative analysis using QSR-NUDIST. The main themes to emerge suggested that patients with a high wish to hasten death had greater concerns with physical symptoms and psychological suffering, perceived themselves to be more of a burden to others, and experienced higher levels of demoralization, while also reporting less confidence in symptom control, fewer social supports, less satisfaction with life experiences and fewer religious beliefs when compared with patients who had a moderate or no wish to hasten death. The implications of these findings will be discussed.

Adult↗

Onset and duration of protective immunity to IA/IB and IE strains of Venezuelan equine encephalitis virus in vaccinated mice.

Three vaccines developed for protection against IA/IB subtypes of Venezuelan equine encephalitis (VEE) virus were evaluated in mice for the ability to protect against systemic and mucosal challenges with a virulent virus of the IE subtype. The vaccines were the formaldehyde-inactivated C-84 and live attenuated TC-83 vaccines currently administered to people under investigational new drug (IND) status, and a new live attenuated vaccine candidate, V3526. V3526 was superior for inducing protection to VEE IA/IB within a week of vaccination, and protection persisted for at least a year. All three vaccines induced long-term clinical protection against peripheral or mucosal challenge with IE virus, with the mucosal immunity induced by attenuated vaccines lasting longer than that induced by the inactivated vaccine. These data show that the molecularly cloned V3526 vaccine induces equivalent or improved immunity to homologous and heterologous VEE viruses than the existing vaccines.

Animals↗

Circles: the replication-recombination-chromosome segregation connection.

Crossing over by homologous recombination between monomeric circular chromosomes generates dimeric circular chromosomes that cannot be segregated to daughter cells during cell division. In Escherichia coli, homologous recombination is biased so that most homologous recombination events generate noncrossover monomeric circular chromosomes. This bias is lost in ruv mutants. A novel protein, RarA, which is highly conserved in eubacteria and eukaryotes and is related to the RuvB and the DnaX proteins, gamma and tau, may influence the formation of crossover recombinants. Those dimeric chromosomes that do form are converted to monomers by Xer site-specific recombination at the recombination site dif, located in the replication terminus region of the E. coli chromosome. The septum-located FtsK protein, which coordinates cell division with chromosome segregation, is required for a complete Xer recombination reaction at dif. Only correctly positioned dif sites present in a chromosomal dimer are able to access septum-located FtsK. FtsK acts by facilitating a conformational change in the Xer recombination Holliday junction intermediate formed by XerC recombinase. This change provides a substrate for XerD, which then completes the recombination reaction.

Amino Acid Sequence↗

Quality of life and oral function in patients treated with radiation therapy for head and neck cancer.

BACKGROUND: Multiple oral complaints develop during radiation therapy for head and neck cancer, and quality of life is affected after treatment. The purpose of this investigation was to assess the quality of life, oral function, and oral symptoms in a cohort of patients during and after radiation therapy. METHODS: A general quality of life survey (the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), with an added oral symptom and function scale was administered to a consecutive series of patients who received radiation therapy for head and neck malignant disease. Patients completed surveys at the beginning of radiation therapy, immediately after, and 6 months after treatment. RESULTS AND DISCUSSION: The questionnaire used in this study provides increased information regarding the oral and dental function that is frequently affected by radiation therapy. Results of this study indicate the need to determine oral dysfunction after head and neck cancer therapy, so that the most predictable cure or best palliation of the malignancy with the least impact on oral function and quality of life is chosen. Oral complications during and after radiation therapy for head and neck cancer are common and affect quality of life. Oral QOL does not return to pretreatment levels by 6 months after radiation therapy. This study supports the use of a general function scale such as the EORTC questionnaire with the addition of disease/site-specific scales to provide data on outcomes of therapy and on the complications associated with therapy. The EORTC QLQ 30 questionnaire with the oral assessment addendum provides a measure of the quality of life and oral function in head and neck cancer patients and may provide useful outcome measures for assessment of oral care prevention and management strategies in these patient populations. The results show that the questionnaire is responsive to change throughout the course of radiation therapy for head and neck cancer.

Adult↗