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Biomedical subjects

M Anderson

Publications and source records attributed to M Anderson.

At least 181 records · Page 10Linked to original sources
PubMed1997

Mental illness and criminal behaviour: a literature review.

The purpose of this paper is to review the current literature in relation to mental illness and criminal behaviour. The material presented for discussion was selected from forensic and general psychiatric literature. However, a number of important publications, policy documents and independent reports were used to explore the debate surrounding this subject. Contemporary studies of prison populations in the UK and abroad illustrated the difficulty in relating mental illness to crime. Papers presenting research in the UK revealed important implications for mental health policy and the way in which the penal system deals with mentally disordered offenders. The literature reviewed provided arguments for and against an association between mental illness and criminal behaviour. Methodological problems associated with criminological and psychiatric research were addressed in relation to the exploration of whether people suffering from a mental illness are more dangerous or violent than other people. Research papers focusing on public reaction to mentally ill people living in the community provided important considerations when addressing mental illness and criminal behaviour in the context of care in the community policy. This paper will be of interest to a broad range of mental health professionals, particularly those working with individuals who have a history of mental illness and violent behaviour, or mental health professionals working with mentally disordered offenders.

Crime↗
PubMed1997

Increasing vancomycin resistance in Enterococcus spp. in Australia: facing the challenge in the laboratory.

High level vancomycin resistance in enterococci (VRE) is increasing in Australia. If the spread of VRE is to be checked, then it is vital for laboratories to be able to detect it promptly and accurately. We have established a rapid and accurate screening method using Enterococcosel agar supplemented with 6 mg/l vancomycin. It can recover VRE from spiked feces, it may be used to screen feces for carriage of VRE and it is not subject to the confounding effects which feces introduce to broth enrichment culture.

Australia↗
PubMed1997

Ambulatory services in an aboriginal community and a west Queensland rural area.

The aim of this study was to compare the incidence/prevalence of diseases in persons attending for ambulatory care at a Queensland Aboriginal community and a farming area in western Queensland. Data were analysed for attendances for disease management from 1 May 1994 to 31 April 1995 at Cherbourg Hospital and from 1 March 1995 to 28 February 1996 at Alpha Hospital. Over these periods the hospitals and associated clinics were the only local ambulatory services available to each community. The numbers of visits for management of disease were 6.0 per person per year at Cherbourg and 4.3 per person per year at Alpha. At each location 78% of the population visited the service for disease management. At Cherbourg, the commonest diagnoses were skin diseases, mainly associated with scabies, accidents and injuries, and respiratory diseases. At Alpha the commonest problems were accidents and injuries, and respiratory disorders, followed by musculoskeletal, skin and CNS disorders. The rate of diabetes was higher in the Cherbourg group, but involved only 5% of the population and was thus not a major cause for the use of health services. The rate of visits for cardiovascular disease at Alpha and Cherbourg were similar, but the percentage of persons involved was smaller at Cherbourg. Accidents and injuries, and respiratory diseases were common in both locations. Skin disease, mainly due to scabies, was a major problem in the Aboriginal community and led to many admissions. Many visits involved potentially preventable diseases.

Adult↗
PubMed1997

SpoVM, a small protein essential to development in Bacillus subtilis, interacts with the ATP-dependent protease FtsH.

The spoVM gene encodes a 26-amino-acid polypeptide that is essential for spore formation in Bacillus subtilis. A transposon insertion within the spoVM open reading frame has been shown to encode a chimeric protein which is biologically inactive and produces a phenotype identical to that of a deletion and insertion mutation. A genetic approach was used to identify possible interacting proteins, and the membrane-bound FtsH protease was identified. Mutations in ftsH suppressed the sporulation defect of certain spoVM mutants but not others. However, production of the mother cell sigma factors, sigmaE and sigmaK, was abnormal in the suppressed strains, and mutations in either spoVM or ftsH alone impaired sigma factor production and sporulation gene expression. Using FtsH purified from Escherichia coli, we demonstrated that in vitro (i) SpoVM inhibits FtsH protease activity and (ii) SpoVM is a substrate for the FtsH protease. We propose that during sporulation, SpoVM serves as a competitive inhibitor of FtsH activity. This interaction appears to be important for completion of the prespore engulfment step of sporulation, based on the phenotype of certain spoVM ftsH double mutants.

ATP-Dependent Proteases↗
PubMed1997

Titrated intravenous opioids from the same syringe: an infection risk?

OBJECTIVE: (1) To compare the rate of contamination of syringes prepared under laminar flow conditions in pharmacy with those prepared by nurses in the emergency department; (2) to determine whether the time elapsed since preparation or number of doses given affected the contamination rate; (3) to determine whether any adverse effects resulted from bacterially contaminated drugs. METHODS: Prospective, blinded trial exploring the effect of method of preparation, time since preparation, and number of doses given on contamination rates and infective adverse events associated with bacterially contaminated specimens. RESULTS: The rate of bacterial contamination was 12% (95% confidence interval 6% to 18%). There was no difference in contamination rate in respect of method of preparation, number of doses given, or time since preparation. No infective complications were identified. CONCLUSIONS: Abandonment of titrated intravenous opioids is not justified by the results. However, there is concern about the use of this technique of pain control for immunocompromised patients and those with prosthetic heart valves.

Analgesia↗
PubMed1997

Listeria endocarditis: current management and patient outcome--world literature review.

This is believed to be the 58th reported case of Listeria monocytogenes infective endocarditis. Published reports worldwide were reviewed as to treatment, outcome, and prognostic features. There is controversy over whether all patients with this condition should have surgery. Moreover the best antibiotic treatment is not known, which accounts for the heterogeneity of regimens used. Listeria endocarditis has a high mortality rate (37%). This was higher in men (41% v 32%) and in patients with valve prostheses (41% v 31%), though neither observation reached statistical significance. There was no significant difference in mortality between surgical and non-surgical treatment, but untreated listeria endocarditis proved universally fatal. From the data, treatment with ampicillin is recommended, with resort to surgery in cases where the infection cannot be eradicated or where haemodynamic compromise has occurred.

Aged↗
PubMed1997

Evaluating the potential effectiveness of using computerized information systems to prevent adverse drug events.

In this study a dynamic computer simulation model is used to estimate the effectiveness of various information systems applications designed to detect and prevent medication errors that result in adverse drug events (ADEs). The model simulates the four stages of the drug ordering and delivery system: prescribing, transcribing, dispensing and administering drugs. In this study we simulated interventions that have been demonstrated in prior studies to decrease error rates. The results demonstrated that a computerized information system that detected 26% of medication errors and prevented associated ADEs could save 1,226 days of excess hospitalization and $1.4 million in hospital costs annually. Those results suggest that such systems are potentially a cost-effective means of preventing ADEs in hospitals. The results demonstrated the importance of viewing adverse drug events from a systems perspective. Prevention efforts that focus on a single stage of the process had limited impact on the overall error rate. This study suggests that system-wide changes to the drug-ordering and delivery system are required to significantly reduce adverse drug events in a hospital setting.

Clinical Pharmacy Information Systems↗
PubMed1996

Paracetamol prescribing habits in a children's hospital.

AIM: Paracetamol is an analgesic/antipyretic widely used in children. The drug can cause hepatic and renal damage due to cumulative toxicity when used in excess of 90 mg/kg@day. There are no dosing guidelines for paracetamol use in children under 1 month of age. We wished to discern current paracetamol prescribing habits in order to establish safety of current practices and offer recommendations towards rational use. METHODS: An anonymous questionnaire was sent to all medical staff working in a university childrenís hospital. We sought information about paracetamol prescribing regimes for children 4 months and over, 3 months and under and neonates in the first 2 weeks of life. Pharmacists audited daily prescription charts of inpatients without hepatic or renal disease over a 2 month period. The maximum possible daily dose was calculated for each child and note was made if a dose in excess of 95 mg/kg was given. RESULTS: There were 53 respondents to the 80 questionnaires posted. There was a trend to use lower daily doses in the younger age group. Similarly, more practitioners either did not use or did not know safe dosing schedules in children 3 months and younger. During the 2 month period there were 823 prescriptions for children 4 months and over, 85 for infants 3 months and under and seven for under 2 week old neonates. In the children 4 months and over 25 of 140 prescriptions exceeding 95 mg/kg/day were given and two of six were given in infants 3 months and younger. CONCLUSION: Many medical staff were unsure of current safe dosing regimens, particularly in the younger age groups. Seventeen percent of prescriptions were above 95 mg/kg/day although only 3% of children were given these doses due to on demand charting and due to audit by pharmacy and nursing staff. There are few guidelines for children 3 months and under. The literature suggests 60-65 mg/kg/day in infants 1-3 months, although this dose was only charted in 16% of prescriptions and phamacokinetic data favours a higher dose. In neonates 30 mg/kg/day achieves effective therapeutic concentrations but further studies are needed.

Acetaminophen↗
PubMed1996

Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase.

We have determined the solution structure of the C-terminal SH2 domain of the p85 alpha subunit of human phosphatidylinositol (PI) 3-kinase (EC 2.7.1.137) in complex with a phosphorylated tyrosine pentapeptide sequence from the platelet-derived growth factor receptor using heteronuclear nuclear magnetic resonance spectroscopy. Overall, the structure is similar to other SH2 domain complexes, but displays different detail interactions within the phosphotyrosine binding site and in the recognition site for the +3 methionine residue of the peptide, the side chain of which inserts into a particularly deep and narrow pocket which is displaced relative to that of other SH2 domains. The contacts made within this +3 pocket provide the structural basis for the strong selection for methionine at this position which characterizes the SH2 domains of PI3-kinase. Comparison with spectral and structural features of the uncomplexed domain shows that the long BG loop becomes less mobile in the presence of the bound peptide. In contrast, extreme resonance broadening encountered for most residues in the beta D', beta E and beta F strands and associated connecting loops of the domain in the absence of peptide persists in the complex, implying conformational averaging in this part of the molecule on a microsecond-to-millisecond time scale.

Amino Acid Sequence↗
PubMed1996

Inhibitors of acyl-CoA:cholesterol O-acyltransferase. synthesis and pharmacological activity of (+/-)-2-dodecyl-alpha-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetrazole-5- acetamide and structurally related tetrazole amide derivatives.

A series of tetrazole amide derivatives of (+/-)-2-dodecyl-alpha-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetrazole-5- acetamide (1) was prepared and evaluated for their ability to inhibit acyl-CoA: cholesterol O-acyltransferase (ACAT) in vitro and to lower plasma total cholesterol in vivo. For this series of compounds, our objective was to systematically replace substituents appended to the amide and tetrazole moieties of 1 with structurally diverse functionalities and assess the effect that these changes have on biological activity. The ensuing structure-activity relationship (SAR) studies identified aryl (7b) and heteroaryl (7f,g) replacements for 2,4,6-trimethoxyphenyl that potently inhibit liver microsomal and macrophage ACAT in vitro and exhibit good cholesterol lowering activity (56-66% decreases in plasma total cholesterol at 30 mg/kg), relative to 1, when compared in the acute rat model of hypercholesterolemia. Replacement of the alpha-phenyl moiety with electron-withdrawing substituents (13e-h), however, significantly reduced liver microsomal ACAT inhibitory activity (IC50 > 1 microM). This is in contrast to electron-donating substituents (13ij,m-q), which produce IC50 values ranging from 5 to 75 nM in the hepatic microsomal assay. For selected tetrazole amides (1, 7b, 13n,o), reversing the order of substituents appended to the 2- and 5-positions in the tetrazole ring (36a-d), in general, improved macrophage ACAT inhibitory activity and provided excellent cholesterol-lowering activity (ranging from 65% to 77% decreases in plasma total cholesterol at 30 mg/kg) in the acute rat screen. The most potent isomeric pair in this set of unsubstituted methylene derivatives (13n and 36a) caused adrenocortical cell degeneration in guinea pigs treated with these inhibitors. In contrast, adrenal glands taken from guinea pigs treated with the corresponding alpha-phenyl-substituted analogs (7b and 36c) were essentially unchanged compared to untreated controls. Subsequent evaluation of 7b and 36c in a rabbit bioassay showed that both compounds and/or their metabolities were present in plasma after oral dosing. Unlike 7b and 36c, compound 1 and related 2,4,6-trimethoxyanilides (13j, 30c,d) showed poor oral activity in the rabbit bioassay. Nevertheless, in cholesterol-fed rabbits, both systemically available (7b, 36c) and poorly absorbed inhibitors (1, 36d) were more effective in lowering plasma total cholesterol than the fatty acid amide CI-976.

Animals↗
PubMed1996

Effect of smoking cessation on cervical lesion size.

BACKGROUND: Cigarette smoking has been postulated as a cofactor in the aetiology of cervical cancer, but a causal role is difficult to establish because of potential confounding by sexual behaviour. We have investigated the effect of cessation or reduction of cigarette smoking on the course of minor-grade cervical lesions. METHODS: In this intervention study 82 women volunteers with minor-grade lesions on colposcopy (cervical intraepithelial neoplasia grade 1 or less) attempted to give up smoking for 6 months. Smoking histories were taken at 3-monthly clinic visits and verified by measurement of salivary cotinine concentrations. At each clinic visit, a photograph of the cervix was taken; the image was digitised and computer-aided image analysis was used to assess lesion size, by investigators unaware of smoking status. FINDINGS: Of the 82 women, 17 stopped smoking completely for at least 6 months and 11 others reduced their smoking consumption by more than 75%. Of these 28 women, 23 (82%) showed a reduction in lesion size of at least 20% or 4 mm2 compared with 13 (28%) of the 47 non-quitters (odds ratio 12.0 [95% Cl 3.9-32.7]). The remaining seven women had unconfirmed smoking histories. There was a significant correlation between the extent of smoking reduction and the change in lesion size (chi2 for trend=31.55, p<0.0001). Adjustment for social class, method of contraception, and stage of menstrual cycle did not affect the results. INTERPRETATION: Our findings support a link between smoking and cervical disease and suggest that smoking cessation could have a beneficial effect on early cervical abnormalities.

Adult↗
PubMed1996

gamma-Glutamyl transpeptidase mediation of tumor glutathione utilization in vivo.

BACKGROUND: Glutathione is a tripeptide used by cells to protect against oxidative and free radical damage. It may also be involved in biochemical mechanisms that cause some tumors to become resistant to anticancer drugs. gamma-Glutamyl transpeptidase (GGTP) is a membrane-bound enzyme that cleaves extracellular glutathione, providing cells with amino acids necessary for intracellular synthesis of this compound. Increased expression of GGTP has been found in a number of human tumors; however, few studies have examined the contribution of GGTP to tumor glutathione metabolism in vivo. PURPOSE: Our goals were to study the utilization of host glutathione by 3-methylcholanthrene (MCA)-induced sarcomas grown in rats and to evaluate the involvement of tumor GGTP in this process. METHODS: The left ovaries of 21 female Fischer 344 rats were isolated by laparotomy and placed in subcutaneous positions through stab wounds in the abdominal wall. A 3-mm cube of MCA sarcoma was then sutured to each of the isolated ovaries. The MCA implants obliterated the ovarian tissue, yielding isolated tumors with one arterial supply (the ovarian artery) and one draining vein (the ovarian vein, referred to as the tumor vein). After 2 weeks of tumor growth, blood was drawn from the tumor vein, the inferior vena cava (IVC), and the aorta of 16 animals. Glutathione and cysteine concentrations in plasma samples from this blood were determined by high-performance liquid chromatography and used to calculate glutathione and cysteine utilization ratios for the tumor and the systemic circulations ([(concentration aorta-concentration tumor vein)/concentration aorta] x 100 and [(concentration aorta-concentration IVC)/concentration aorta ] x 100, respectively). The utilization ratios from these control animals were compared with those from acivicin (AT-125; an irreversible GGTP inhibitor)-treated rats (the remaining five animals). Data are presented as mean +/- standard deviation; reported P values are from two-tailed tests of statistical significance. RESULTS: In the control animals, glutathione and cysteine concentrations were significantly lower in the tumor vein (3.55 +/- 1.9 and 5.69 +/- 2.8 microM, respectively) and in the IVC (5.65 +/- 2.3 and 7.17 +/- 2.4 microM, respectively) than in the artery (12.48 +/- 5.7 and 12.33 +/- 5.9 microM, respectively; all P values < .05). In addition, the glutathione utilization ratio was significantly higher for the tumor circulation than for the systemic circulation (69% +/- 14% versus 52% +/- 14%; P < .003). The combined glutathione and cysteine utilization ratio was also significantly higher for the tumor circulation than for the systemic circulation (116% +/- 35% versus 88% +/- 28%; P < .02). Treatment with AT-125 lowered the tumor glutathione utilization ratio significantly (45% +/- 12% for treated animals versus 69% +/- 14% for control animals; P < .005). CONCLUSIONS: Our results show that glutathione and cysteine in the host circulation are used by MCA sarcomas. The significant reduction in tumor utilization of serum glutathione after treatment with AT-125, a GGTP inhibitor, indicates that GGTP is important in tumor glutathione metabolism.

Animals↗
PubMed1996

Dipyridamole mediated enhanced antiproliferative activity of 10-ethyl-10-deazaaminopterin (10-EDAM) against human lung cancer cell lines.

10-ethyl-10-deazaaminopterin (10-EDAM) is a rationally designed derivative of the antifolate, methotrexate (MTX). In a number of tumor models these design features have resulted in an improved spectrum of antiproliferative activity as compared with the parent compound. Using an MTT growth assay, we compared in vitro antiproliferative activity of 10-EDAM with MTX in eight lung cancer cell lines. Growth was inhibited in all lines tested by clinically achievable concentrations of 10-EDAM (0.1-1,000 nM). 10-EDAM was more cytotoxic than MTX at the same concentrations in all eight lung cancer cell lines. In an effort to enhance the antiproliferative effect, we evaluated the addition of dipyridamole (DPM), an inhibitor of nucleoside transport, to 10-EDAM (0.1-10 microns). DPM decreased the concentration of 10-EDAM required to cause 50% growth inhibition (IC50) in all eight cell lines tested. This suppression was statistically significant by 2-sided sign test (P = .0078). By contrast, the IC50 of MTX was decreased in only two of the eight cell lines when DPM was added (0.1-10 microM). In defined thymidine depleted media, cell kill by the combination of 10-EDAM and DPM was no greater than 10-EDAM alone, consistent with the possibility that DPM exerts some of its effect by inhibition of extrinsic nucleoside salvage. In consideration of the published activity of 10-EDAM in lung cancer and the modest clinical toxicity of DPM based biochemical modulation, we conclude the current in vitro data provide justification for clinical evaluation of this combination in patients with lung cancer.

Aminopterin↗