Drug-related admissions due to interaction with an old drug, lithium.

Lithium is one of the oldest psychotropic drugs with a well-known narrow therapeutic range and the drugs that interact with lithium elimination are well established. However, patients are still admitted to the emergency department with lithium toxicity due to often overlooked interactions with concomitant drugs. We report on two patients, admitted to the emergency department, with lithium toxicity. One patient presented with aphasia and ataxia, showing moderate toxicity. The other was referred due to coma, illustrating severe lithium toxicity. In both cases, a non-steroidal anti-inflammatory drug was the underlying cause. We highlight the mechanism of this drug-drug interaction and underline the need for thoughtful use of other medications in patients taking lithium. Special attention has to be paid for the non-steroidal antiinflammatory drugs due to the low threshold of prescribing them for the control of acute pain and its availability as free over-the-counter drugs.

Metformin-associated lactic acidosis (MALA): case report.

Metformin is the first-line therapy for the treatment of diabetes mellitus. In certain conditions lactic acidosis (MALA) can occur. Starting with a case report of a 62-year-old woman presenting with abdominal pain, we bring this complication to attention, describing its pathogenesis and its management. This underlines the need for thoughtful use of metformin.

[How to improve the continuity of pharmacotherapy at hospital admission and discharge]. / Comment optimiser la continuité du traitement médicamenteux entre l'hôpital et le domicile?

The continuity of pharmacotherapy is of vital importance when patients move from one health care setting to another. Unfortunately, this continuity is not always guaranteed. The aim of this study is to propose solutions to enhance the continuity of pharmacotherapy at hospital admission and discharge. The study consists of a systematic review of the international literature and an analysis of seamless care initiatives in seven selected countries; a summary of Belgian data on problems as well as solutions with regard to continuity of care; a quantification of the extent of medication changes as a result of a hospital stay in Belgium; and a qualitative analysis of the perception of Belgian health care professionals (HCPs) on approaches to improve seamless care. The literature review yielded 15 papers of sufficient quality. However, this review did not generate definitive conclusions on the clinical impact and the cost-effectiveness of interventions aiming to enhance the continuity of pharmacotherapy. The most important initiatives that have been put in practice in foreign countries include the development and implementation of guidelines for HCPs; national information campaigns; education of HCPs; and the development of information technologies as to share patient and prescription data between settings of care. For Belgium, 66 seamless care initiatives were identified. The high number and variety of projects show the interest for this topic as well as the involvement of various HCPs from diverse settings in the development of solutions. Based on this research, and the solutions discussed in the focus groups, the following elements are proposed to enhance the continuity of pharmacotherapy: a national guideline governing the continuity of pharmacotherapy; a national campaign to sensitize HCPs and patients in this area; the availability of a comprehensive and up to date medication list for each patient; and electronic healthcare infrastructure that facilitates sharing of information.

SPRR4, a novel cornified envelope precursor: UV-dependent epidermal expression and selective incorporation into fragile envelopes.

The cornified cell envelope (CE), a structure formed in the outermost layers of stratified squamous epithelia, provides a physical barrier against environmental insults. It is composed of several structural proteins, which are irreversibly crosslinked by calcium-activated transglutaminases. The small proline rich proteins (SPRRs) are one set of CE precursors. SPRR4, a novel member of this gene family, displayed very low or undetectable expression levels in normal human skin or other stratified squamous epithelia, but was clearly induced by UV light both in vivo and in vitro. High epidermal expression of SPRR4 was monitored only after chronic UV exposure and was concomitant with a thickening of the stratum corneum, which is believed to provide protection against subsequent damage. The calcium-dependent translocation of an SPRR4-GFP fusion protein to the cell periphery in living keratinocytes and its integration into both rigid and fragile cornified envelopes proved that SPRR4 is a novel CE precursor. Interestingly, after UV irradiation, SPRR4 was selectively incorporated into fragile CEs. Our results show for the first time that UV-induced cornification is accompanied by qualitative changes in CE precursor assembly. SPRR4 is part of an adaptive tissue response to environmental stress, which is likely to compensate for UV induced impairment of the epidermal barrier function.

Presence of immunoreactive beta-endorphin in human skin.

The production and its induction by ultraviolet radiation (UVR) of proopiomelanocortin (POMC)-derived peptides by keratinocytes has been reported, albeit not consistently. Recently we demonstrated that only under specific culturing conditions human keratinocytes are capable of producing a beta-endorphin (betaE)-like peptide with the characteristics of beta-lipotropin (betaLPH). Here the presence and UV-induction of betaE-immunoreactivity (betaE-IR) in keratinocytes in human skin in vivo was investigated. betaE-IR was detectable by immunohistochemistry in keratinocytes of the follicular matrix and to some extent in cells of sweat ducts, but was absent from epidermal keratinocytes. Absence of betaE-IR was confirmed by radioimmunoassay of HPLC-fractionated extracts of normal epidermis. Repeated exposure to solar-simulated UVR had no effect. This investigation is the first to demonstrate the presence of betaE-immunoreactive material in the follicular matrix of corporal hairs and in duct cells of sweat glands. The possible meaning of these results is discussed.

Solar-simulated skin adaptation and its effect on subsequent UV-induced epidermal DNA damage.

Repeated skin exposure to ultraviolet radiation leads to increased tolerance for erythema. Whether this tolerance is accompanied by a significant protection against epidermal DNA injury has never been thoroughly investigated. In a first set of experiments we irradiated 25 healthy volunteers three times a week for 3 wk using solar-simulating tanning lamps. In addition, all individuals were exposed to a (challenge) dose of three times the initial minimal erythema dose on a small area of skin before the first and after the final exposure. On both occasions, cyclobutane pyrimidine dimers were quantified in biopsies. As expected, repeated ultraviolet exposures resulted in increased epidermal pigmentation and thickness. The ultraviolet sensitivity for erythema decreased on average by 75%. The cyclobutane pyrimidine dimer formation was reduced on average by 60%. In a second set of experiments, with a group of 13 subjects, DNA repair kinetics were assessed. Within a period of 5 d after a single, slightly erythemal dose (1.2 minimal erythema dose), levels of cyclobutane pyrimidine dimer and p53-expressing cells were determined in skin biopsies. Both markers of DNA damage were elevated upon the single ultraviolet exposure and returned to background levels after 3-4 d. This information is important when trying to minimize the risk of DNA damage accumulation after repeated exposures during a tanning course.

[Tanning beds: effect on skin cancer risk unclear]. / Zonnebanken: onduidelijk effect op huidkankerrisico.

Recent estimations show that over 25% of the Dutch population make regular use of tanning equipment. This use is still increasing, in spite of improving knowledge on the potential hazards of ultraviolet radiation. There are different motivations to use the tanning equipment. Younger women are largely represented in the group of sunbed users. Recent studies have brought the testimony that intermittent sun exposure (e.g. during holidays) is an important risk factor for skin cancer (notably basal cell carcinoma and melanoma). The investigations have not provided convincing evidence on the relation between the use of artificial devices and the development of skin cancer. This is partly caused by the fact that sunbed users are generally very motivated to get a tan. It is therefore difficult to distinguish between the effect of natural sun and of artificial UV radiation. In the Netherlands, the analyses of scientific data provide the basis for recommendations concerning sun exposure and use of sunbeds. There is an effort to provide the general public with qualified, professional information on the responsible way of tanning.