Effects of a drug overdose in a television drama on presentations to hospital for self poisoning: time series and questionnaire study

ObjectivesTo determine whether a serious paracetamol overdose in the medical television drama Casualty altered the incidence and nature of general hospital presentations for deliberate self poisoning.DesignInterrupted time series analysis of presentations for self poisoning at accident and emergency departments during three week periods before and after the broadcast. Questionnaire responses collected from self poisoning patients during the same periods.Setting49 accident and emergency departments and psychiatric services in United Kingdom collected incidence data; 25 services collected questionnaire data.Subjects4403 self poisoning patients; questionnaires completed for 1047.ResultsPresentations for self poisoning increased by 17% (95% confidence interval 7% to 28%) in the week after the broadcast and by 9% (0 to 19%) in the second week. Increases in paracetamol overdoses were more marked than increases in non-paracetamol overdoses. Thirty two patients who presented in the week after the broadcast and were interviewed had seen the episode—20% said that it had influenced their decision to take an overdose, and 17% said it had influenced their choice of drug. The use of paracetamol for overdose doubled among viewers of Casualty after the episode (rise of 106%; 28% to 232%).ConclusionsBroadcast of popular television dramas depicting self poisoning may have a short term influence in terms of increases in hospital presentation for overdose and changes in the choice of drug taken. This raises serious questions about the advisability of the media portraying suicidal behaviour.

Key messages

• This study found that portrayal of self poisoning in a popular television drama was associated with a short lived increase in presentation of self poisoning patients to general hospitals
• Choice of substance taken in overdose was also influenced by the broadcast
• Extreme caution should be exercised about portraying suicidal behaviour on television, and especially about giving details of the method used
• The potential role of television in preventing suicidal behaviour requires investigation

     

Effects of cellular pharmacology on drug distribution in tissues.

The efficacy of targeted therapeutics such as immunotoxins is directly related to both the extent of distribution achievable and the degree of drug internalization by individual cells in the tissue of interest. The factors that influence the tissue distribution of such drugs include drug transport; receptor/drug binding; and cellular pharmacology, the processing and routing of the drug within cells. To examine the importance of cellular pharmacology, previously treated only superficially, we have developed a mathematical model for drug transport in tissues that includes drug and receptor internalization, recycling, and degradation, as well as drug diffusion in the extracellular space and binding to cell surface receptors. We have applied this "cellular pharmacology model" to a model drug/cell system, specifically, transferrin and the well-defined transferrin cycle in CHO cells. We compare simulation results to models with extracellular diffusion only or diffusion with binding to cell surface receptors and present a parameter sensitivity analysis. The comparison of models illustrates that inclusion of intracellular trafficking significantly increases the total transferrin concentration throughout much of the tissue while decreasing the penetration depth. Increasing receptor affinity or tissue receptor density reduces permeation of extracellular drug while increasing the peak value of the intracellular drug concentration, resulting in "internal trapping" of transferrin near the source; this could account for heterogeneity of drug distributions observed in experimental systems. Other results indicate that the degree of drug internalization is not predicted by the total drug profile. Hence, when intracellular drug is required for a therapeutic effect, the optimal treatment may not result from conditions that produce the maximal total drug distribution. Examination of models that include cellular pharmacology may help guide rational drug design and provide useful information for whole body pharmacokinetic studies.     

Effects of self medication programme on knowledge of drugs and compliance with treatment in elderly patients.

OBJECTIVE--To determine whether a programme of self medication for inpatients improves compliance with treatment and knowledge of their drugs after discharge from hospital. DESIGN--Patients were prospectively recruited from four wards: two with a self medication programme and two acting as controls. Ten days after discharge the patients were visited at home. They were questioned about their drugs, and a tablet count was undertaken. SETTING--The pharmacy department and four medical wards with an interest in elderly patients at a district general hospital, and the patients'' homes. PATIENTS--88 patients discharged to their own homes who were regularly taking one or more drugs. INTERVENTION--A hospital self medication programme in which patients are educated about their medicines and given increasing responsibility for taking them in hospital. MAIN OUTCOME MEASURES--Compliance with and knowledge of the purpose of their medicines 10 days after discharge from hospital. RESULTS--The mean compliance score in patients taking part in the self medication programme was 95% compared with 83% in the control group (difference 12%, 95% confidence interval 4% to 21%; P < 0.02). Of the patients in the self medication group, 90% (38/42) knew the purpose of their drugs compared with 46% (17/37) in the control group (difference 44%, 26% to 63%; P < 0.001). CONCLUSION--A self medication programme is an effective aid for improving compliance with and knowledge of patients'' drugs after discharge.     

Trehalose-6-P synthase is dispensable for growth on glucose but not for spore germination in Schizosaccharomyces pombe.

Trehalose-6-P inhibits hexokinases in Saccharomyces cerevisiae (M. A. Blázquez, R. Lagunas, C. Gancedo, and J. M. Gancedo, FEBS Lett. 329:51-54, 1993), and disruption of the TPS1 gene (formerly named CIF1 or FDP1) encoding trehalose-6-P synthase prevents growth in glucose. We have found that the hexokinase from Schizosaccharomyces pombe is not inhibited by trehalose-6-P even at a concentration of 3 mM. The highest internal concentration of trehalose-6-P that we measured in S. pombe was 0.75 mM after heat shock. We have isolated from S. pombe the tps1+ gene, which is homologous to the Saccharomyces cerevisiae TPS1 gene. The DNA sequence from tps1+ predicts a protein of 479 amino acids with 65% identity with the protein of S. cerevisiae. The tps1+ gene expressed from its own promoter could complement the lack of trehalose-6-P synthase in S. cerevisiae tps1 mutants. The TPS1 gene from S. cerevisiae could also restore trehalose synthesis in S. pombe tps1 mutants. A chromosomal disruption of the tps1+ gene in S. pombe did not have a noticeable effect on growth in glucose, in contrast with the disruption of TPS1 in S. cerevisiae. However, the disruption prevented germination of spores carrying it. The level of an RNA hybridizing with an internal probe of the tps1+ gene reached a maximum after 20 min of heat shock treatment. The results presented support the idea that trehalose-6-P plays a role in the control of glycolysis in S. cerevisiae but not in S. pombe and show that the trehalose pathway has different roles in the two yeast species.     

Effects of testosterone on the behaviour of the domestic chick. I. Effects present in males but not in females.

In male chicks, specific facilitation of male copulatory movements occurs at a lower dosage of testosterone oenanthate than does facilitation of approach to the test object, or of attack. The latter effects can be dissociated in other ways from the first; they may depend upon a single central change in visual responsiveness or persistence. Females show none of these changes, although they are capable of the behaviour patterns involved, and do show other behavioural effects of testosterone. On day 3 normal males copulate and attack more, and flee less than do females.     

Envelope glycoprotein gp50 of pseudorabies virus is essential for virus entry but is not required for viral spread in mice.

Phenotypically complemented pseudorabies virus gp50 null mutants are able to produce plaques on noncomplementing cell lines despite the fact that progeny virions are noninfectious. To determine whether gp50 null mutants and gp50+gp63 null mutants are also able to replicate and spread in animals, mice were infected subcutaneously or intraperitoneally. Surprisingly, both gp50 mutants and gp50+gp63 double mutants proved to be lethal for mice. In comparison with the wild-type virus, gp50 mutants were still highly virulent, whereas the virulence of gp50+gp63 mutants was significantly reduced. Severe signs of neurological disorders, notably pruritus, were apparent in animals infected with the wild-type virus or a gp50 mutant but were much less pronounced in animals infected with a gp50+gp63 or gp63 mutant. Immunohistochemical examination of infected animals showed that all viruses were able to reach, and replicate in, the brain. Examination of visceral organs of intraperitoneally infected animals showed that viral antigen was predominantly present in peripheral nerves, suggesting that the viruses reached the central nervous system by means of retrograde axonal transport. Infectious virus could not be recovered from the brains and organs of animals infected with gp50 or gp50+gp63 mutants, indicating that progeny virions produced in vivo are noninfectious. Virions that lacked gp50 in their envelopes, and a phenotypically complemented pseudorabies virus gII mutant (which is unable to produce plaques in tissue culture cells), proved to be nonvirulent for mice. Together, these results show that gp50 is required for the primary infection but not for subsequent replication and viral spread in vivo. These results furthermore indicate that transsynaptic transport of the virus is independent of gp50. Since progeny virions produced by gp50 mutants are noninfectious, they are unable to spread from one animal to another. Therefore, such mutants may be used for the development of a new generation of safer (carrier) vaccines.     

The AP-1 sequence is necessary but not sufficient for phorbol induction of collagenase in fibroblasts.

Collagenase, the only enzyme active at neutral pH that initiates collagen degradation, is a major gene product of fibroblasts that have been stimulated with a variety of agents, including phorbol esters. To study mechanisms controlling collagenase gene expression, we transiently transfected rabbit synovial fibroblasts with chimeric constructs containing up to 1.2 kb of the rabbit collagenase 5'-flanking DNA linked to the chloramphenicol acetyltransferase gene (CAT). Our data indicate that the magnitude of the phorbol response is directly linked to the size of the promoter fragment and that the smallest piece of promoter DNA conferring phorbol inducibility is 127 bp. Deletional and mutational analysis of this fragment revealed that the AP-1 sequence alone is insufficient for phorbol inducibility and the presence of at least two additional sequences (a PEA3-like element and a sequence that includes 5'-TTCA-3') is required. In addition, a substantial increase in responsiveness is seen when a fragment containing 182 bp of 5'-flanking DNA is transfected, implicating a 36 bp region located between -182 and -149 as an enhancer. We conclude (1) that the AP-1 sequence is necessary but insufficient for expression of collagenase in adult fibroblasts, (2) that phorbol inducibility depends on cooperation among several sequence elements within the collagenase promoter, and (3) that regulation of this promoter is more complex than previously described.     

Glycine 100 in the dinitrogenase reductase of Rhodospirillum rubrum is required for nitrogen fixation but not for ADP-ribosylation.

Dinitrogenase reductase (Rr2) is required for reduction of the molybdenum dinitrogenase in the nitrogen fixation reaction and is the target of posttranslational regulation in Rhodospirillum rubrum. This posttranslational regulation involves the ADP-ribosylation of Rr2. To study the structural requirements for these two functions of Rr2, i.e., activity and regulation, two site-directed mutations in nifH, the gene encoding Rr2, were constructed and analyzed. The mutations both affected a region of the protein known to be highly conserved in evolution and to be relevant to both of the above properties. These mutants were both Nif-, but one of the altered Rr2s was a substrate for ADP-ribosylation. This demonstrates that the ability of Rr2 to participate in nitrogen fixation can be separated from its ability to act as a substrate for ADP-ribosylation.     

The leader polypeptide of Theiler's virus is essential for neurovirulence but not for virus growth in BHK cells.

A leader polypeptide of unknown function is encoded by cardioviruses, such as Theiler's murine encephalomyelitis virus. Although the deletion of this polypeptide has little effect on the growth of parental GDVII virus in baby hamster kidney (BHK) cells, the mutant virus is completely attenuated and fails to kill mice receiving intracerebral inoculations of high doses of the virus.