The Effects of Serum from Patients with Acute Liver Failure on the Growth and Metabolism of Hep G2 Cells

In many bioartificial liver systems currently being designed and evaluated for use in fulminant hepatic failure, direct contact is required between the patient's blood and the liver cells in the device. The efficacy of such devices will be influenced by the interaction of fulminant hepatic failure (FHF) patient serum with the cells. We have found that FHF serum inhibits the growth rate and the synthesis of DNA, RNA, and protein; disturbs glutathione homeostasis; and induces morphological changes in cultured human Hep G2 cells. These interactions should influence the design of bioartificial liver devices based on proliferating cell lines and indicate the requirement to pretreat FHF patient plasma to reduce the toxin load.     

The preclinical evaluation of the water vapour transmission rate through burn wound dressings

The control of evaporative water loss, following burn injury, is of major importance to the overall condition of the patient, whether this control is by natural eschar or by a dressing. It is therefore important to preclinically determine the water vapour transmission rate of these dressings, firstly to make comparisons between different materials and secondly to screen prototype materials, under controlled conditions. A preclinical (in vitro) technique is described and the results are given for several commercially available dressings which encompass foam, film and hydrogel material categories.     

Comparison of cancer risk estimates based on a variety of risk assessment methodologies

The EPA guidelines recommend a benchmark dose as a point of departure (PoD) for low-dose cancer risk assessment. Generally the PoD is the lower 95% confidence limit on the dose estimated to produce an extra lifetime cancer risk of 10% (LTD(10)). Due to the relatively narrow range of doses in two-year bioassays and the limited range of statistically significant tumor incidence rates, the estimate of the LTD(10) is constrained to a relatively narrow range of values. Because of this constraint, simple, quick estimates of the LTD(10) can be readily obtained for hundreds of rodent carcinogens from the Carcinogenic Potency Database (CPDB) of Gold et al. Three estimation procedures for LTD(10) are described, using increasing information from the CPDB: (A) based on only the maximum tolerated dose (the highest dose tested); (B) based on the TD(50); and (C) based on the TD(50) and its lower 99% confidence limit. As expected, results indicate overall similarity of the LTD(10) estimates and the value of using additional information. For Method (C) the estimator based on the [[(TD(50))(0.36) x (LoConf)(0.64)]/6.6] is generally similar to the estimator based on the one-hit model or multistage model LTD(10). This simple estimate of the LTD(10) is applicable for both linear and curved dose responses with high or low background tumor rates, and whether the confidence limits on the TD(50) are wide or tight. The EPA guidelines provide for a margin of exposure approach if data are sufficient to support a nonlinear dose-response. The reference dose for cancer for a nonlinear dose-response curve based on a 10,000-fold uncertainty (safety) factor from the LTD(10), i.e., the LTD(10)/10,000, is mathematically equivalent to the value for a linear extrapolation from the LTD(10) to the dose corresponding to a cancer risk of <10(-5) (LTD(10)/10,000). The cancer risk at <10(-5) obtained by using the q(1)(*) from the multistage model, is similar to LTD(10)/10,000. For a nonlinear case, an uncertainty factor of less than 10,000 is likely to be used, which would result in a higher (less stringent) acceptable exposure level.     

Correlation of blood cholinesterase levels with toxicity of sarin in rats

The dose-mortality response curve for sarin when administered to pregnant rats is extremely steep. The pregnant animal either died during the treatment or survived with no observable fetal toxicity. Animals that died displayed many symptoms characteristic of anticholinesterase toxicity. The present study was conducted to determine whether the maternal deaths, clinical observations, and/or weight loss could be correlated with baseline blood cholinesterase levels in individual animals. Cholinesterase levels (plasma and erythrocyte) were obtained prior to, during, and following treatment of nonpregnant rats by gavage with 380 microg/kg/d sarin for 10 d. After the first dose, there was a drop in the plasma cholinesterase levels, which then remained low throughout the dosing period. There was a statistically significant correlation between body weight loss and plasma cholinesterase levels of the sarin dosed animals. The surviving animals also had lower plasma cholinesterase levels and lower body weights, both of which recovered on the cessation of dosing. The erythrocyte cholinesterase levels were not different between treated and nontreated rats. Neither plasma or erythrocyte baseline cholinesterase levels nor relative or absolute cholinesterase decline values could be used as predictors of mortality from sarin administration in rats.     

Comparison of teratogenic and carcinogenic risks

Risk assessment for teratogens has received much less attention than carcinogens. This may be due in part to the lack of biologically based dose-response models for teratogens. Also, there appears to be a perception that cancer risks far exceed teratogenic risks for most chemicals. This perception may be due in large part to the stringent practice of using conservative procedures to restrict cancer risk estimates to one in 100,000 or lower whereas procedures used to restrict teratogens may result in much higher risks. The purpose of this paper is to compare estimates of teratogenic and carcinogenic risks for chemicals when both effects occur in the same animal species. Similar procedures are employed here to obtain teratogenic and carcinogenic risk estimates for nine chemicals. When a similar standard of risk is applied to both effects, the relative potency of teratogens to carcinogens varied from an order of magnitude lower to an order of magnitude higher for these nine chemicals.     

Clinical activities of an academic pediatric pharmacy team

BACKGROUND: Pharmacy school faculty, residents, and students have been shown to positively impact patient care in multiple settings. However, their potential role in the care of pediatric patients has not been described. OBJECTIVE: To document the contribution of pharmacy school faculty, residents, and students to the optimization of medical care for pediatric patients. METHODS: All clinical interventions performed by faculty, residents, and students for pediatric patients seen from January through December 2002 were recorded and analyzed. The interventions were concurrently recorded using a handheld and desktop computer-based documentation system, the Pharmacist's Electronic Database for Interventions, developed by the pediatric practice team. Practice sites included general pediatrics, pediatric intensive care, neonatal intensive care, and ambulatory clinics. RESULTS: Four faculty members, 5 residents, and 44 students collected intervention data. A total of 4605 interventions were performed for 3978 patients. The most common interventions performed were drug therapy change, pharmacokinetic monitoring, drug information, and medication histories/patient education. Drug added and drug deleted were the most frequent interventions performed in the drug therapy change category. The most common indications for which interventions were made were infectious (39.6%) and respiratory (23.3%) diseases. A total of 223 adverse drug events or medication errors were prevented or detected during the study period. Errors in dosing (overdose or underdose) were the most commonly encountered adverse events. CONCLUSIONS: Pharmacy school faculty, residents, and students perform numerous clinical activities that play a significant role in the multidisciplinary care of pediatric patients.     

Understanding what helps or hinders asthma action plan use: a systematic review and synthesis of the qualitative literature

Objective

To understand better what helps and/or hinders asthma action plan use from the professionals and patients/carers perspective.

Methods

Systematic review and qualitative synthesis (using meta-ethnography).

Results

Nineteen studies (20 papers) were included in an analysis of patients/carers’ and professionals’ views. Seven main influences on action plan implementation were identified including perceived un-helpfulness and irrelevance of the plans. Translation and synthesis of the original authors’ interpretations suggested that action plan promotion and use was influenced by professional and patient/carers’ asthma beliefs and attitudes and patient/carer experiences of managing asthma. Action plan use is hindered because professionals and patients/carers have different explanatory models of asthma, its management and their respective roles in the management process. Patients/carers, based on their experiential knowledge of their condition, perceive themselves as capable, effective in managing their asthma, but health professionals do not always share this view.

Conclusion

Professionally provided medically focused action plans that do not ‘fit’ with and incorporate the patients’/carers’ views of asthma, and their management strategies, will continue to be under-utilised.

Practice implications

Professionals need to develop a more patient-centred, partnership-based, approach to the joint development and review of action plans, recognising the experiential asthma knowledge of patients/carers.