Short-term effects of propranolol on portal venous pressure

The present study was designed to investigate the effect of propranolol on portal pressure of patients with alcoholic cirrhosis and portal hypertension and to correlate these effects with clinical and laboratory parameters. The mean baseline hepatic venous pressure gradient in the 50 patients studied was of 18.2 +/- 4.1 mm Hg. It decreased significantly 2 hr after the oral administration of 40 mg of propranolol to 15.7 +/- 4.2 mm Hg (a mean reduction of 13.4 +/- 17%). This reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure. There was no correlation between the decrease in hepatic venous pressure gradient and the decrease in heart rate. When results were analyzed individually, only 15 (30%) showed a large decrease in hepatic venous pressure gradient (greater than 20%), 15 (30%) showed a moderate decrease (10 to 19%), and in 20 patients (40%) there was no reduction or an increase in hepatic venous pressure gradient. Comparison of "responders" (those that reduced hepatic venous pressure gradient greater than 10%) and "nonresponders" (hepatic venous pressure gradient reduction less than 10%) showed no significant differences in baseline laboratory and hemodynamic parameters, in the severity of the liver disease, in the heart rate and blood pressure response to propranolol, nor in the propranolol plasma levels achieved 2 hr after propranolol administration. Propranolol plasma levels correlated with the reduction in heart rate but not with the reduction in hepatic venous pressure gradient. Of 14 nonresponders to 40 mg of propranolol who received additional doses, six showed a reduction in hepatic venous pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Establishing and managing a periodontal biobank for research: the sharing of experience

Periodontal bio‐repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad‐based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.     

Isolation and partial characterization of a cholesterol-requiring mutant of Chinese hamster ovary cells.

A sterol-requiring mutant has been isolated from mutagenized Chinese hamster ovary cells. This mutant grows normally only when cholesterol is present in the medium. Cell lysis occurs within 3 days in the absence of cholesterol. The frequency of reversion of this mutant to prototrophic growth is low (less than or equal to 10(-6). Whole cell pulse experiments with [14C]acetate or [3H]mevalonate indicate that the rate of synthesis of digitonin-precipitable material is greatly diminished in the mutant cells as compared to that in normal Chinese hamster ovary cells. Enzyme assays in vitro with crude cell extracts show that the biosynthetic conversion of mevalonate to squalene and the conversion of squalene to lanosterol are not impaired in the mutant cells. Gas-liquid chromatographic analyses of radioactive sterol composition after whole cell pulse experiments with [3H]squalene and with [3H]anosterol suggest that the fundamental enzymatic defect of the mutant is at the stage of lanosterol demethylation. When cells were grown in serum-free medium, lanosterol and dihydrolanosterol accumulated intracellularly in the mutant cells before cell lysis occurred; neither of these two intermediary sterols was detected in the wild-type cells grown under the same condition.     

In Vitro Conversion of Estradiol-Receptor Protein to Its Nuclear Form: Dependence on Hormone and DNA

Early events in the action of 17-beta-estradiol can be studied in soluble extracts of rat uterus by exposure of the estradiol-receptor protein to a DNA-cellulose matrix. After complexing with [(3)H]estradiol, the 4S receptor protein binds to the DNA, and it can be eluted with buffer of high ionic strength as a more tightly binding, 5S form. This parallels the in vivo situation, where migration of the receptor to the nucleus follows addition of hormone and is concomitant with a similar increase in sedimentation rate to 5 S. In both cases, the formation of a 5S receptor requires the presence of 17-beta-estradiol. The rate at which 5S receptor forms is sensitive to extract concentration in a way that suggests that this receptor is a complex created by addition of a second subunit to the hormone-binding 4S component; physical studies on both in vivo and in vitro 5S receptors also support this view. These results are interpreted in terms of a model for action of estrogen in which the hormone potentiates binding of receptor to DNA, and in turn, the DNA-binding process triggers the cell response.     

Mandatory Procedures and Fairness in Mental Impairment Hearings

Uncertainty has attended procedures for adjudging unfitness to stand trial in Victoria pursuant to the Crimes (Mental Impairment and Unfitness to be Tried) Act 1997 (Vic) and how “special hearings” should be conducted when a person is determined to be unfit to stand trial but does not wish to pursue the defence of not guilty because of mental impairment. In R v Langley [2008] VSCA 81, (2009) 19 VR 90 the Victorian Court of Appeal clarified the procedures to be employed at jury trials on such matters and quashed a decision not in conformity with proper procedures, making clear that denial of fairness to such accused persons has the potential to result in appealable error.     

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.     

Sexual Surrogate Partner Therapy: Legal and Ethical Issues

The Ben Lewin film The Sessions has drawn attention again to the potential role for sexual surrogate partners and sex workers in enabling persons with disabilities and impairments to give expression to their sexual needs and desires. However, away from the big screen, the ethics of registered health practitioners in themselves engaging in such therapies are highly problematic. Difficult too is the role of such practitioners in being ‘the therapist’ responsible for enabling or brokering sexual contact between their patients and those offering such services for financial reward. In some jurisdictions, arrangements involving sexual surrogate therapy (especially where the therapist benefits from it financially) may not be lawful. Further, in spite of many assertions one way and the other, there are no data enabling evaluation of the success rates of the interventions of sexual surrogates or sex workers. Whether positive outcomes to such interactions are likely in most circumstances, given that the provision of services is predicated upon idealised attachments, is questionable. It is also unclear whether sexual surrogates’ adherence to an ethical code effectively ameliorates the potential for counter-therapeutic consequences from the commodification of intimacy, and it is far from straightforward to identify what steps should be taken by the referring health practitioner to select a suitable provider of sexual services to their patient or client, and then to monitor whether the arrangement is achieving its objectives.