Human Rights and Review of the Involuntary Status of Patients with a Mental Illness: Kracke after Momcilovic

Arguably, Australia's most significant judicial pronouncement on the human rights of those with mental illnesses was made in 2009 by Justice Bell, the then President of the Victorian Civil and Administrative Tribunal (“VCAT”). The decision is an exhaustive analysis of the application of the Charter of Human Rights and Responsibilities Act 2006 (Vic) to the involuntary status of a person subject to a community treatment order in Victoria. It occurred in the context of delays in the conduct of reviews of the status of a mentally ill person by Victoria's Mental Health Review Board (“the Board”). The outcome of the hearing was a declaration that the Board had breached the person's human rights to a fair hearing, even though the person's involuntary status on a community treatment order was not disturbed by VCAT. Whilst some important aspects of Justice Bell's decision concerning the general methodology to be applied when analysing human rights were overturned in the subsequent Court of Appeal decision of R v Momcilovic [2010] VSCA 50, the latter decision did not concern mental health and so leaves Kracke as the most detailed articulation and analysis of human rights within this difficult sphere.     

Arg-Gly-Asp-dependent occupancy of GPIIb/IIIa by applaggin: evidence for internalization and cycling of a platelet integrin

Using indirect immunofluorescence microscopy we examined the distribution and cycling of GPIIb/IIIa after binding to applaggin, a high-affinity Arg-Gly-Asp (RGD)--containing ligand. Resting, unfixed platelets were incubated with applaggin for 30 minutes at 37 degrees C, and bound applaggin was detected by an affinity-purified rabbit anti- applaggin antibody. Examination of intact cells showed a rim pattern for applaggin, consistent with its binding to the platelet surface. Staining of Triton X-100--permeabilized cells showed an intracellular pool of applaggin. Competition of applaggin binding by either AP-2, an anti-GPIIb/IIIa monoclonal antibody (MoAb) that blocks fibrinogen binding, or the synthetic peptide RGDW eliminated both surface and intracellular staining, indicating that applaggin is binding to GPIIb/IIIa in an RGD-dependent manner. Inhibition of platelet activation by PGE1 and theophylline had no effect on the observed staining patterns, indicating that cellular activation is not required for surface binding and subsequent internalization. To evaluate whether occupancy of functional binding sites on GPIIb/IIIa is required for internalization, we used mAb15, an anti-GPIIIa antibody that neither blocks fibrinogen binding nor induces the expression of ligand-induced binding sites on GPIIb/IIIa. In these studies mAb15 was internalized in a manner analogous to both AP-2 and applaggin, showing that occupancy of the RGD binding site is not required to initiate receptor internalization. To estimate the size of the newly internalized pool of applaggin, 125I-applaggin--binding studies were performed. Displacement of bound 125I-applaggin by excess unlabeled applaggin or EDTA showed that at least 17% of bound applaggin was nondisplaceable when binding was performed under conditions permitting membrane flow and internalization. These data indicate that GPIIb/IIIa is internalized in unstimulated platelets independent of cellular activation or occupancy of the functional binding site(s) of GPIIb/IIIa by RGD-containing ligands. Thus, internalization of GPIIb/IIIa may represent a mechanism by which the surface expression of this adhesion receptor is regulated.     

Interleukin-3, GM-CSF, and TPA induce distinct phosphorylation events in an interleukin 3-dependent multipotential cell line

The mechanism of action of the hemopoietic growth factor, murine interleukin-3 (mIL-3), was investigated using an mIL-3-dependent multipotential hematopoietic cell line, B6SUtA1. Murine granulocyte- macrophage colony-stimulating factor (mGM-CSF) was as potent as mIL-3 in stimulating these cells. In addition, sodium orthovanadate, an inhibitor of phosphotyrosine phosphatase, and 12-O-tetradecanoyl- phorbol-13-acetate (TPA), a known activator of protein kinase C, also stimulated DNA synthesis in these cells, suggesting that protein phosphorylation might be involved in the mechanism of action of mIL-3 and mGM-CSF. To assess this possibility, intact B6SUtA1 cells exposed for brief periods to mIL-3, mGM-CSF, and TPA were analyzed for changes in phosphorylation patterns using metabolic 32P-labeling and antibodies to phosphotyrosine. Both mIL-3 and mGM-CSF induced the serine-specific phosphorylation of a 68-Kd cytosolic protein, whereas all three agents stimulated the serine-specific phosphorylation of a 68-Kd membrane protein. Furthermore, mIL-3 stimulated tyrosine phosphorylation of the 68-Kd membrane protein, as well as of 140-, 90-, 55, and 40-Kd proteins. The 90-Kd protein was also tyrosine phosphorylated in response to mGM-CSF. These phosphotyrosine containing proteins were not detected in TPA-treated cells. These results indicate that protein phosphorylations on tyrosine and serine residues occur in B6SUtA1 cells following short-term incubation with mIL-3 or mGM-CSF and that most of these phosphorylation events are mediated by kinases other than protein kinase C (PkC).     

Giant Asian honeybee or Bambara stings causing myocardial infarction,bowel gangrene and fatal anaphylaxis in Sri Lanka: a case series

The sting of Giant Asian honeybee (Apis dorsata) or Bambara in Sinhala and Karunge Kulavi in Tamil is a common environmental hazard in Sri Lanka known to cause immediate allergic reactions, which could be fatal in sensitized individuals. We reported myocardial infarction, bowel gangrene and fatal anaphylaxis in a prospectively proven case series and the association of these uncommon complications with delayed removal of stingers from the patients' skin.     

选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。     

MGB1 Poor Adherence to Hypertension Treatment Guidelines: An Analysis of Therapeutic Choices

The recent Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) reiterated long-standing recommendations that Stage 1 hypertension (BP ≥ 140/90 mm Hg) without comorbidity should be treated initially with diuretics (DI) or beta blockers (BB). Yet market research suggests that many physicians prefer to use other drug classes, such as calcium channel blockers and ACE inhibitors.
OBJECTIVES: To explore the determinants of therapeutic choice in hypertension.
METHODS: We surveyed by mail a stratified random sample of 10,000 U.S. cardiologists, internists, and family/general practitioners. Physicians were queried about their practice environment and their knowledge, attitudes, and practices regarding antihypertensive therapy, including their choice of drugs to treat patients with specified clinical profiles. The probability that physicians would follow JNC guidelines Stage 1 hypertension was analyzed using multiple logistic regression with stepwise backward elimination to select variable with p < 0.001.
RESULTS: Completed surveys were received from 1,023 physicians. 86.7% prescribe drug therapy for Stage 1 hypertension, and 19.5% (22.5% of drug prescribers) limit their choices to DI and BB. Guideline conformity was higher among physicians who: practice in academic medical centrers; are older; are general practitioners (versus general internists); have smaller caseloads; have fewer hypertensive patients; have higher proportions of HMO, Medicaid, and uninsured patients; and experience more formulary restrictions. Cardiologists and family practitioners were less likely than internists to follow guidelines.
CONCLUSION: JNC guidelines are better accepted by academic physicians, older physicians who have more expenence using DI and BB, physicians with smaller caseloads and hence more time for follow-up and therapy adjustment, and physicians who face drug reimbursement constraints.     

Demography of sleep disturbances associated with circadian rhythm disorders in Japan

To clarify the demography of delayed sleep phase syndrome (DSPS), non-24-h sleep-wake syndrome, and irregular sleep-wake pattern in Japan, a cross-sectional nationwide epidemiological survey was conducted. 1525 adults (age: 15-59 years) were randomly sampled from telephone directories, and they received screening questions over the phone. Persons who were suspected of having the disorders were requested to fill out the second questionnaire, and asked to keep a sleep log for 4 weeks. Diagnoses were made according to the International Classification of Sleep Disorders criteria. As a result, the prevalence of DSPS was estimated to be 0.13%.