Developing genetic privacy legislation: the South Carolina experience.

The availability of presymptomatic and predisposition genetic testing has spawned the need for legislation prohibiting health insurance discrimination on the basis of genetic information. The federal effort, the Health Insurance Portability and Accountability Act (HIPAA) of 1996, falls short by protecting only those who access insurance through group plans. A committee of University of South Carolina professionals convened in 1996 to develop legislation in support of genetic privacy for the state of South Carolina. The legislation prevents health insurance companies from denying coverage or setting insurance rates on the basis of genetic information. It also protects the privacy of genetic information and prohibits performance of genetic tests without specific informed consent. In preparing the bill, genetic privacy laws from other states were reviewed, and a modified version of the Virginia law adopted. The South Carolina Committee for the Protection of Genetic Privacy version went a step further by including enforcement language and excluding Virginia's sunset clause. The definition of genetic information encompassed genetic test results, and importantly, includes family history of genetic disease. Our experience in navigating through the state legislature and working through opposition from the health insurance lobby is detailed herein.

Echocardiographic assessment of left ventricular mass and systolic function in mice.

The increasing use of transgenic mouse models for investigating the mechanisms of cardiac growth and function has made it important to develop noninvasive methods for assessing murine cardiac anatomy, size, and function. At present, murine cardiac mass can be determined only at necropsy. Left ventricular (LV) function can be assessed by use of various catheterization techniques, but these approaches are usually terminal procedures and provide no information about chamber anatomy and dimensions. Although transthoracic echocardiography has been used to study the LVs of rats and larger animals, the considerably smaller LV masses and somewhat faster heart rates of mice pose significant challenges to obtaining good-quality echocardiograms. In this study we tested the hypothesis that transthoracic echocardiography can image the murine LV as well as provide assessments of LV mass and function. Our results in a series of 33 mice, including normal, transgenic, and aortic-banded subgroups, demonstrate the capability of transthoracic two-dimensionally directed M-mode echocardiography in mice to (1) obtain good-quality images, (2) produce estimates of LV mass having good correlations with directly determined LV mass in normal mice, (3) detect LV hypertrophy noninvasively in different experimental models, and (4) identify impaired LV systolic function. Thus, echocardiography appears to be a promising approach for noninvasively assessing LV mass and function in mice.

Prescription-event monitoring of 10,401 patients treated with fluvoxamine.

Prescription-event monitoring (PEM) is one of two national systems of drug safety monitoring practised in Britain. The objective of this PEM study was to assess the safety of fluvoxamine and to monitor the occurrence of untoward and other events during treatment. A total of 10,401 patients treated with the drug in general practices throughout England were studied and data were analysed in the Drug Safety Research Unit, Southampton. The main outcome measures were the overall incidence of events per 1000 patients; the incidence during the first month of treatment; the mean incidence for months 2-6 of treatment; and the ratio of these rates as a signal that an event could be drug related. The most commonly reported category of events was neuropsychiatric while the most commonly reported individual events were nausea and vomiting. Fluvoxamine was shown to be a safe drug and no unexpected or previously undetected drug-related events were encountered. There was a relatively high incidence of gastro-intestinal symptoms, but other adverse reactions often encountered during treatment with tricyclic antidepressants were not frequently reported.

Assessment of epileptogenic potential: experimental, clinical and epidemiological approaches.

There are experimental, clinical and epidemiological methods of assessing the epileptogenic potential of psychotropic drugs. In the laboratory it has been shown that there is a range of cellular and synaptic processes in the cerebral cortex and hippocampus that give rise to epileptiform neuronal activity. In addition to the classical suppression of GABA-mediated inhibitory synaptic mechanisms, in vitro studies in animal models of epilepsy and on human tissue suggest a prominent role for the N-methyl D-aspartate (NMDA) subtype of excitatory amino acid receptors. Any mechanism that leads to the depolarization of the neurones is likely to result in a facilitation of the NMDA-receptor involvement in excitatory neurotransmission. This is particularly true in the cortex and hippocampus where the densities of the NMDA-receptor are highest. Data are presented in this paper on how this epileptogenic mechanism can be studied in vitro. In humans, the importance of an accurate diagnosis is stressed and the advantages and disadvantages of routine EEG recordings and ambulatory monitoring discussed. Descriptions of large-scale systems of drug safety monitoring and their application to the assessment of the epileptogenic properties of psychotropic drugs are given.

A longitudinal assessment of renal function during treatment with lithium.

Renal function was studied during lithium treatment in 28 patients on two occasions separated by a mean interval of 4.7 years. Glomerular filtration rate, assessed by creatinine clearance and serum creatinine concentrations, showed no impairment. Albumin excretion rate, a marker of glomerular permeability, showed no consistent change. In contrast, a decline in urine concentrating ability (mean 140 mOsm/kg) was found in all patients, exceeding the reduction to be expected from ageing in all but three. These results support the view that treatment with lithium long-term does not damage renal glomerular function, but that progressive impairment of the distal tubular responsiveness to arginine vasopressin is common.

Adverse effects of antianxiety drugs.

Antianxiety drugs, like other drugs used in psychiatry, can cause a wide range of adverse effects. Many physiological systems may be affected, but, as the main action of antianxiety drugs is on the central nervous system, this system is particularly vulnerable. All antianxiety drugs have the potential to produce untoward effects on higher cerebral functions, although the effect seen is also influenced by psychological and social factors. The most common effects is oversedation, which is a particular problem for the very young and the very old. It is also a serious problem for those who drive motor vehicles and may be a hazard when working in dangerous situations. Subjects are especially vulnerable when (a) antianxiety drugs are first introduced; (b) the dose is increased; and (c) these agents are taken in combination with alcohol and other drugs. Dependence on antianxiety drugs is well known, but only recently has it been recognised that dependence on benzodiazepines is a larger problem than previously realised. Other adverse effects are reviewed and summarised according to the system they predominantly affect. A review of this kind can easily give a biased impression of the dangers of antianxiety drugs; it should be made clear at the outset that many effects are rare, and in some instances a causal connection with the drug has not been established with certainty. Overall, benzodiazepines are the most widely used of all drugs and are remarkably safe-even when taken in massive overdoses. Some unwanted effects are readily preventable if antianxiety drugs are used with caution or avoided altogether in conditions where pathological disturbances of tissue sensitivity or drug disposition lead to exaggerated reactions. Particular care should be taken when prescribing these drugs for children and the elderly, and drugs that are not clearly essential for the well-being of the mother should be avoided during pregnancy and breast feeding. Antianxiety agents are grossly overprescribed. The frequency of occurrence of some adverse effects is therefore not so much a manifestation of the intrinsic toxicity of antianxiety drugs, but a reflection of their widespread use. Overprescribing and irrational prescribing also contribute to self-poisoning with these and other agents and to the cost of health services. The reasons for overprescribing are complex, but one contributing factor is the ready availability of effective antianxiety drugs.