Increased health care utilization and increased antiretroviral use in HIV-infected individuals with mental health disorders

Objectives The aims of the study were to describe the prevalence and associations of mental health disorder (MHD) among a cohort of HIV-infected patients attending the Victorian HIV/AIDS Service between 1984 and 2000, and to examine whether antiretroviral therapy use or mortality was influenced by MHD (defined as a record of service provision by psychiatric services on the Victorian Psychiatric Case Register). It was hypothesized that HIV-positive individuals with MHD would have poorer treatment outcomes, reduced responses to highly active antiretroviral therapy (HAART) and increased mortality compared with those without MHD. Methods This is a retrospective cohort of 2981 individuals (73% of the Victorian population diagnosed with HIV infection) captured on an HIV database which was electronically matched with the public Victorian Psychiatric Case Register (VPCR) (accounting for 95% of public system psychiatry service provision). The prevalence, dates and recorded specifics of mental health disorders at the time of the electronic match on 1 June 2000 are described. The association with recorded MHD, gender, age, AIDS illness, HIV exposure category, duration and type of antiviral therapy, treatment era (prior to 1986, post-1987 and pre-HAART, and post-HAART) on hospitalization and mortality at 1 September 2001 was assessed. Results Five hundred and twenty-five individuals (17.6% of the Victorian HIV-positive population) were recorded with MHD, most frequently coded as attributable to substance dependence/abuse or affective disorder. MHD was diagnosed prior to HIV in 33% and, of those diagnosed after HIV, 93.8% were recorded more than 1 year after the HIV diagnosis. Schizophrenia was recorded in 6% of the population with MHD. Hospitalizations for both psychiatric and nonpsychiatric illness were more frequent in those with MHD (relative risk 5.4; 95% confidence interval 3.7, 8.2). The total number of antiretrovirals used (median 6.4 agents vs 5.5 agents) was greater in those with MHD. When adjusted for antiretroviral treatment era, HIV exposure category, CD4 cell count and antiretroviral therapy, survival was not affected by MHD. Conclusions MHD is frequent in this population with HIV infection and is associated with increased healthcare utilization but not with reduced survival.

Blockade of the C5a receptor fails to protect against experimental autoimmune encephalomyelitis in rats

Complement activation contributes to inflammation and tissue damage in human demyelinating diseases and in rodent models of demyelination. Inhibitors of complement activation ameliorate disease in the rat model antibody-dependent experimental autoimmune encephalomyelitis and rats unable to generate the membrane attack complex of complement develop inflammation without demyelination. The role of the highly active chemotactic and anaphylactic complement-derived peptide C5a in driving inflammation and pathology in rodent models of demyelination has been little explored. Here we have used a small molecule C5a receptor antagonist, AcF-[OPdChaWR], to examine the effects of C5a receptor blockade in rat models of brain inflammation and demyelination. C5a receptor antagonist therapy completely blocked neutrophil response to C5a in vivo but had no effect on clinical disease or resultant pathology in either inflammatory or demyelinating rat models. We conclude that C5a is not required for disease induction or perpetuation in these strongly complement-dependent disease models.

Antiretrovirals as antimalarial agents

Recent studies have indicated that antiretroviral protease inhibitors may affect outcome in malarial disease. We have investigated the antimalarial activities of 6 commonly used antiretroviral agents. Our data indicate that, in addition to the previously published effects on cytoadherence and phagocytosis, the human immunodeficiency virus (HIV)-1 protease inhibitors saquinavir, ritonavir, and indinavir directly inhibit the growth of Plasmodium falciparum in vitro at clinically relevant concentrations. These findings are particularly important in light of both the high rate of malaria and HIV-1 coinfection in sub-Saharan Africa and the effort to employ highly active antiretroviral therapy in these regions.

Alveolar haemorrhage in anti-glomerular basement membrane disease without detectable antibodies by conventional assays

Anti-glomerular basement membrane (anti-GBM) disease represents the spectrum of disease attributable to circulating anti-GBM antibodies. While active anti-GBM disease in the absence of circulating anti-GBM antibodies has been described, it is considered rare with the use of current routinely available assays. We report four subjects with features consistent with active anti-GBM antibody disease without detectable antibodies by routinely available enzyme linked immunosorbent assay (ELISA) and immunoblot techniques. All were smokers who presented with diffuse alveolar haemorrhage, minimal renal involvement, and undetectable anti-GBM antibodies. Seronegative anti-GBM disease with predominant pulmonary involvement may be more common than previously appreciated and should be part of the differential diagnosis for otherwise unexplained diffuse alveolar haemorrhage. Renal biopsy with immunofluorescent studies should be considered in the diagnostic evaluation of such subjects, including those with idiopathic pulmonary haemosiderosis.

Why is Coccidoxenoides perminutus, a mealybug parasitoid, ineffective as a biocontrol agent - Inaccurate measures of parasitism or low adult survival?

Coccidoxenoides perminutus achieves only low levels of parasitism of its host Planococcus citri in southeast Queensland citrus. Two possible causes were investigated. Adult survival under natural conditions was assessed to determine whether providing adult food sources could enhance survival. Behavioural changes of hosts, induced by C perminutus parasitism, was also investigated to establish if parasitised P. citri move from their feeding site to seek protected shelters some distance away and are thus not accounted for in field assessments of parasitism rates. Unparasitised mealybugs placed in the field for two periods were retrieved before the effects of parasitism were manifested and parasitism rates were still low (0.3% at 5 days and 1.2% at 10 days). Levels of locomotion of P. citri exposed to C perminutus were compared with those of unexposed ones. Parasitised mealybugs, regardless of instar, undergo behavioural changes. In comparison to unparasitised controls, the mealybugs become highly active 7-14 days after exposure to wasps. All parasitised mealybugs undergo physical changes, their body becomes cylindrical, their legs go so rigid that the mealybugs become immobile, and this signifies the typical mummy appearance. All mealybugs that became mummies eventually fell from the host lemon fruit because of impaired locomotion and were caught on sticky traps that had been placed beneath the lemons. Consequently, their final site of mummification was not established. C perminutus adults provided with nectar or honey survived longer (about 5 days) in the field than those without food (about a day). Nectar from two plant species, Alpinia zerumbet and Datura candida, proved to be good sources of food for the adult wasps, and were comparable in quality to honey. The low level of parasitism achieved by C perminutus in southeast Queensland citrus thus appears to be a consequence of the short adult life and the negative effects of a harsh environment. Provision of a suitable food source (e.g., nectar) may well enhance levels of parasitism in the field. (c) 2005 Elsevier Inc. All rights reserved.

Prostanoids as friends, not foes: Further evidence from the interference by cycloxygenase-inhibitory drugs when inducing tolerance to experimental arthritigens in rats

Pharmacologists have generally been prejudiced against prostanoids, uncritically accepting their suppression as desirable therapy, especially for ‘quick-fix’ analgesia. This myopic perception for a long time ignored (a) the essentiality of prostanoid precursors in nutrition, (b) the physiological protective functions of natural prostaglandins (PGs) (vasculature, stomach, kidney), (c) resolution of inflammation after the expression of COX-2 and (d) increasing therapeutic use of either synthetic PGs (for erectile dysfunction, opthalmic disorders, inducing parturition, etc) or their natural precursors, e.g., ω3-rich polyunsaturated oils, to treat arthritis. Experimental studies in rats have indicated that prostaglandins (E series) are (i) useful, perhaps auto-regulators of established immunoreactivity and (ii) able to amplify (or even induce) anti-inflammatory activity with other agents. Furthermore, anti-prostanoid therapy (APT) can be arthritigenic!!, interfering with the acquisition of tolerance to some arthritigens. For patients with rheumatoid arthritis this additional side-effect of APT, barely recognised to date, may actually perpetuate their arthritis by impairing prostanoid-mediated remission processes. Hopefully, recent adverse publicity about COX-2 inhibitory drugs might stimulate serious re-assessment of some traditional anti-inflammatory therapies with low APT activity for the management of both acute pain (non-addictive cannabinoids, celery seed, etc.) and chronic inflammation, e.g., Lyprinol® (a mussel lipid extract).

Effects of care pathways on stroke care practices at regional hospitals

Background: Our previous work identified deficiencies in stroke care practices at regional hospitals in comparison to standards suggested by published stroke care guidelines. These deficiencies might be improved by the implementation of clinical pathways. The aim of this study was to assess changes in acute stroke care practices following the implementation of stroke care pathways at four regional Queensland hospitals. Methods: The medical records of two cohorts of 120 patients with a discharge diagnosis of stroke or transient ischaemic attack were retrospectively audited before and after implementation of stroke care pathways to identify differences in the use of acute interventions, investigations and secondary prevention strategies. Results: Following pathway implementation there were clinically important, but not statistically significant, increases in the rates of swallow assessment, allied health assessment (significant for occupational therapy, P = 0.04) and use of deep vein thrombosis prevention strategies (also significant, P = 0.006). Fewer patients were discharged on no anti-thrombotic therapy (statistically significant in the subgroup of patients with atrial fibrillation, P = 0.02). Only 37% of the patients audited were actually enrolled on the pathway. Among this subgroup there were significant increases in the rates of swallow assessment (first 24 h, P = 0.01; any time during admission, P = 0.0001), allied health assessments (all P < 0.05), estimation of blood glucose level (P = 0.0015) and the use of deep vein thrombosis prevention strategies (P = 0.0003). Conclusion: Stroke care pathways appear to improve the process of care. Whether this influences outcomes such as mortality, functional and neurological recovery, the incidence of complications, length of stay or the cost of care was beyond the scope of this study and will require further examination.

Evaluation of oestrogen and progesterone receptor status in HER-2 positive breast carcinomas and correlation with outcome

Aim: HER-2/neu amplification occurs in 15-25% of breast carcinomas. This oncogene, also referred to as c-erbB-2, encodes a transmembrane tyrosine kinase receptor belonging to the epidermal growth factor receptor family. HER-2 over-expression is reported to be associated with a poor prognosis in breast carcinoma patients and in some studies is associated with a poorer response to anti-oestrogen therapy. These patients are less likely to benefit from CMF (cyclophosphamide, methotrexate, fluorouracil)-based chemotherapy compared with anthracycline-based chemotherapy. The aim of this study was to evaluate breast carcinomas to determine hormone receptor status and if there is a difference in breast cancer specific survival for HER-2 positive patients. Methods: A total of 591 breast carcinomas were evaluated using immunohistochemistry (IHC) for oestrogen receptor (ERp), progesterone receptor (PRp) and three different HER2 antibodies (CB11, A0485 and TAB250). Percentage of tumour cells and intensity of staining for ERp were evaluated using a semiquantitative method. Results: Of the 591 tumours, 91 (15.4%) showed 3+ membrane staining for HER-2 with one or more antibodies. Of these 91 tumours, 41 (45.1%) were ERp+/ PRp+, seven (7.7%) were ERp+/PR-, six (6.6%) were ERp-/PRp+ and 37 (40.7%) were ERp-/PR-. Of HER-2 positive tumours, 5.5% showed > 80% 3+ staining for ERp compared with 31.8% of 0-2+ HER-2 tumours; 24.2% of HER-2-positive tumours showed 60% or more cells with 2+ or 3+ staining for ERp. Treatment data were available for 209 patients and no difference was observed in breast cancer specific survival (BCSS) with HER-2 status and tamoxifen. Conclusion: Oestrogen receptor status cannot be used to select tumours for evaluation of HER-2 status, and oestrogen and progesterone receptor positivity does not preclude a positive HER-2 status. There is a higher proportion of ERp negative tumours associated with HER-2 positivity, however, more than 20% of HER-2 positive tumours show moderate or strong staining for ERp. HER-2 positive patients in this study did not show an adverse BCSS with tamoxifen treatment unlike some previous studies.

Anti-proliferative effects of novel Glyco-lipid-arsenicals (III) on MCF-7 human breast cancer cells

Arsenic trioxide appears to be effective in the treatment of pro-myelocytic leukaemia. The substituted phenylarsen(III)oxides are highly polar, they have a high tendency to undergo oxidation to As (V) and to form oligomers, to prevent this we protected the As-(OH)2 group as cyclic dithiaarsanes. To increase the compound's biological stability and passive diffusion we conjugated the compound of interest with lipoamino acids (Laas). Alternatively, we further conjugated the dithiaarsane derivative with a carbohydrate to utilize active transport systems and to target compound. We investigated two novel glyco-lipid arsenicals (III) (compounds 9 and 11) for their ability to initiate MCF-7 breast cancer cell death and characterized the mechanism by which death was initiated. A significant decrease in MCF-7 cell proliferation was observed using 1 μM and 10 μM compound (11) and 10 μM of compound (9). Treatment with compound (11) triggered apoptosis of MFC-7 cells while compound (9) induced inhibition of cellular proliferation was not via rapid induction of apoptosis and more likely reflected necrosis and/ or alterations in the cell cycle. Differences in the anti-proliferative potency of the two compounds indicate that structural modifications influence effectiveness. © 2006 Bentham Science Publishers Ltd.

Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy

Molecular fragments of cartilage are antigenic and can stimulate an autoimmune response. Oral administration of type II collagen prevents disease onset in animal models of arthritis but the effects of other matrix components have not been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix proteins (CaP) from cartilage for a) mitigating disease activity in rats with collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b) stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA were established in Wistar rats using standard methods. Agents were administered orally (10–200 mg/kg), either for seven days prior to disease induction (toleragenic protocol), or continuously for 15 days after injecting the arthritigen (prophylactic protocol). Joint swelling and arthritis scores were determined on day 15. Histological sections of joint tissues were assessed post-necropsy. In chondrocyte cultures, CaP + / − interleukin-1 stimulated PG biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20 mg/kg in the rat CIA model using the toleragenic protocol. It was only active at 20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA toleragenic protocol at 20 mg/kg but chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in the rat AIA model was less than in the CIA model. These findings lead us to suggest that oral CaP could be used as a disease-modifying anti-arthritic drug.

Anti-tumor necrosis factor therapy: The Australian experience

Anti-tumor necrosis factor (TNF) therapy for the management of rheumatic diseases has been reimbursed in Australia progressively per agent and disease indication since 2003. Initial projections of uptake were grossly overestimated. In this article the anti-TNF experience in Australia is reviewed, including results of an eligibility study, Australian Rheumatology Association guidelines, anti-TNF registry, and a report of adverse effects. These observations may assist APLAR countries currently coming to terms with anti-TNF drug registration and funding.