Patterns and predictors of re-admission to hospital with self-poisoning in Scotland.

OBJECTIVES: To identify factors influencing hospital re-admission with self-poisoning. STUDY DESIGN: Retrospective cohort follow-up study using national linked hospital discharge data. METHODS: All Scottish adult hospital episodes with self-poisoning admissions were captured using NHS Scotland Information Services Division data, and first-time 'index' admissions between 1996 and 2002 were identified. Re-admission rate was defined as the proportion of index admissions who went on to have one or more further self-poisoning admissions within 2 years. The effects of various potential risk factors for re-admission were examined using logistic regression. RESULTS: In total, 50,891 index admissions were identified; of these, 8278 patients were re-admitted. The 1-year re-admission rate was 12.2%. Older patients (>65 years) were least likely to be re-admitted [odds ratio (OR) 0.40, P<0.01, compared with patients aged 15-24 years]. No differences were found between males and females. Previous psychiatric hospital admission was associated with an increased re-admission rate (OR 2.85, P<0.01), with a diagnosis of personality disorder associated with the highest rate of re-admission (OR 4.59, P<0.01). Other factors predicting re-admission were: increased deprivation (quintile 3: OR 1.16, P<0.01; quintile 5: OR 1.15, P<0.01, compared with quintile 1); taking medicines for chronic disease, drug dependency (OR 1.6 and 1.19, P < or = 0.02) or antidepressants (OR 1.11, P=0.01) (compared with paracetamol); and co-ingestion of three or more agents (OR 1.37, P<0.01). CONCLUSION: Younger age, higher deprivation, ingestion of certain drug groups or multiple drug types, and prior psychiatric hospital admission are all risk factors for re-admission with self-poisoning. Personality disorder carried the greatest risk of re-admission. These findings may provide a basis to develop policies to reduce re-admission rates in the future.

Poisons admissions in Edinburgh 1981-2001: agent trends and predictors of hospital readmissions.

Self-poisoning is a major public health problem. This study describes patterns of admissions and readmissions from self-poisoning to the Royal Infirmary of Edinburgh from 1981 to 2001. A database on hospital discharges with a diagnosis (ICD-9/10) of poisoning between 1981 and 2001 was used. Annual admissions were described for seven main drug categories, and proportions of patients readmitted within 1-5 years from first admission, were computed for each category. Cox proportional hazards regression was used to evaluate prognostic factors for readmission risk over 1981-2001. For both sexes, admissions increased from the early to mid 1990s, and declined thereafter. The proportion readmitted varied with the drug taken at first admission, from 11.9% (95% CI: 10.8-13%) for non-opiate analgesics, to 17.6% (16.5-18.7%) for benzodiazepines. Deprivation was positively related to readmission risk after first admissions with paracetamol (P < 0.001) and benzodiazepines (P < 0.001). Timing of first admissions involving paracetamol (P < 0.01), benzodiazepines (P < 0.001), antidepressants (P < 0.001), non-opiate analgesics (P < 0.001), and opiates (P < 0.05), was inversely associated with readmission risk. In patients admitted for drug overdose, readmission risk is influenced by type of drug taken at first admission. Information on drug type used in self-poisoning may assist in identifying patients at risk for future events, and in reducing hospital readmissions.

Cloning and characterization of a microsomal aminopeptidase from the intestine of the nematode Haemonchus contortus.

In order to characterise the integral membrane glycoprotein H11 from the intestinal microvilli of the nematode Haemonchus contortus, cDNA libraries prepared using mRNA from adult worms from the UK and Australia were immunoscreened with anti-H11 sera. Antibodies affinity purified on the protein expressed by insert DNA (295 bp) of a positive clone from a UK library bound specifically to H11. A longer clone (948 bp) was obtained from the Australian library by hybridisation. Using a primer based on sequence common to these, a polymerase chain reaction product of 3.3 kb was generated from cDNA from UK H. contortus. The sequences from the UK and Australian nematodes were essentially identical over the 929 bp region in which both were represented. All three cloned DNAs hybridised to mRNA of about 3.5 kb. Analysis of the deduced amino acid sequence, which showed 32% identity with those of mammalian microsomal aminopeptidases, indicated that H11 has a short N-terminal cytoplasmic tail, a single transmembrane region and a long extracellular region with putative N-linked glycosylation sites and the HEXXHXW motif characteristic of microsomal aminopeptidases. Microsomal aminopeptidase activity co-purifies with H11. It is inhibited by bestatin, phenanthroline and amastatin. The recombinant protein has been expressed in active form in insect cells.

A 2359-base pair DNA fragment from Cryptosporidium parvum encoding a repetitive oocyst protein.

A Cryptosporidium parvum lambda gt11 expression library was constructed using EcoRI-digested genomic DNA extracted from in vitro-excysted oocysts. Screening of this library with rat anti-Cryptosporidium antiserum led to the isolation of a clone containing a 2359-bp EcoRI fragment. When this fragment was ligated into the EcoRI site of plasmid vector pMS1S, the resulting clone expressed a 200-kDa beta-galactosidase fusion protein. Western blot analysis using serum raised against this fusion protein indicated that the EcoRI fragment represented part of a gene encoding a 190-kDa oocyst wall protein of C. parvum. Sequencing of the fragment revealed a continuous open reading frame encoding 786 amino acids. The DNA sequence is relatively low in G+C (39.1%), and the third codon position contains only 17.9% G+C. The deduced peptide sequence has unusually high proportions of cysteine, proline, glutamine and histidine. Another striking feature of the amino acid sequence is the presence of distinctly repetitive regions based on conserved cysteine residues.

Effects of ET(A) - and ET(B)-receptor antagonists on regional kidney blood flow, and responses to intravenous endothelin-1, in anaesthetized rabbits.

OBJECTIVE: To determine the roles of endothelin (ET)-receptor subtypes in the effects of exogenous and endogenous ETs on regional kidney blood flow in anaesthetized rabbits. DESIGN AND METHODS: The effects on regional kidney blood flow of the ET(A) antagonist BQ610, and the ET(B) antagonist BQ788, were tested. We also examined the effects of intravenous and renal arterial bolus doses of ET-1, and how these responses are modified by pretreatment with BQ610 and BQ788. RESULTS: BQ610 reduced mean arterial pressure (MAP, 3%), and increased total renal blood flow (RBF, 10%), cortical perfusion (CBF, 11%) and medullary perfusion (MBF, 16%). BQ788 increased MAP (6%) and reduced RBF (16%) and CBF (13%) but not MBF. The effects of BQ788 were abolished by pretreatment with BQ610. Intravenous ET-1 (300 ng/kg) reduced RBF and CBF, but increased MBF. BQ788 potentiated ET-1 mediated reductions in CBF, and abolished increases in MBF. BQ610 blunted reductions in RBF and CBF produced by ET-1, but did not significantly affect MBF responses. The renal vascular effects of intravenous ET-1 were mimicked by lower doses (1-30 ng/kg) administered into the renal artery. CONCLUSIONS: Endogenous ETs act at ET(A)-receptors to reduce MBF and CBF, but ET(B)-receptors have little direct role in physiological control of renal haemodynamics. Bolus doses of ET-1 act at ET(B)-receptors in the kidney to increase MBF. The effects of bolus ET-1 on the cortical vasculature appear to result from the competing influences of ET(A)-mediated vasoconstriction and ET(B)-mediated vasodilatation.

Differences in the immune responses of mice and sheep to an aromatic-dependent mutant of Salmonella typhimurium.

A live mutant aroA Salmonella serotype Typhimurium ovine strain (S25/1) could be cultured from tissues of mice for up to 90 days after oral infection. Following vaccination, high levels of Salmonella-specific serum IgM, IgG and IgA were produced in addition to high levels of specific intestinal IgA. Moreover, there was also evidence of Salmonella-specific cell-mediated immunity in vaccinated mice in the form of strong delayed-type hypersensitivity and the production of interferon-gamma (IFN-tau) by spleen cells stimulated with Salmonella antigen. The aroA strain was also recovered from the mesenteric lymph nodes and most tissues examined from sheep vaccinated by the oral route. Salmonella-specific IgM was detected in the serum; however, specific IgG responses were very low and there was an absence of specific copro-antibody. Although strong Salmonella-specific lymphocyte proliferative responses were detected, they did not result in the production of IFN-tau and flow cytometric analysis revealed that the proliferating cells were predominantly B lymphocytes. Despite the absence of strong vaccine-specific immune responses in vaccinated sheep compared with those seen in mice, both mice and sheep were protected against challenge with virulent wild-type strain S25/1.

In vitro studies with lymphocytes from sheep orally inoculated with an aromatic-dependent mutant of Salmonella typhimurium.

It was previously shown that a live aroA-strain of Salmonella typhimurium of ovine origin was a safe and effective vaccine against salmonellosis in sheep. The protective effect was observed in the apparent absence of a detectable, systemic T cell response. In the present study, populations of B and T cells from the peripheral blood of sheep vaccinated with S25/1aroA were separated and their responsiveness in vitro to Salmonella was examined. The purified T cells proliferated very weakly in response to Salmonella in the absence of interferon-gamma and interleukin 2/4 production. However, whole peripheral blood mononuclear cells and purified B cells proliferated strongly in response to Salmonella, and Salmonella-specific IgM antibodies could be detected in cell supernatants. Furthermore, Salmonella-specific IgM-producing cells were detected at low frequency by enzyme linked immunospot techniques. These observations extend the earlier findings that oral vaccination with S25/1aroA primes predominantly antigen-specific B cells in the absence of strong Salmonella-specific T cell responses.

Venlafaxine poisoning complicated by a late rise in creatine kinase: two case reports.

Newer anti-depressants are often considered to be safer than more established anti-depressants. However, clinical experience of the effects of these agents in overdose is limited. Here, we present two cases of venlafaxine overdose that were complicated by a delayed rise in plasma creatine kinase. Although the clinical consequences were not serious, physicians should be alerted to the possibility of delayed rhabdomyolysis or serotonin syndrome in patients who have taken venlafaxine in overdose.

Growth factors in CNS repair and regeneration.

Traumatic central nervous system (CNS) injury is a significant clinical problem in the developed world. After injuries that penetrate into either the mature brain or spinal cord, damaged neurons initially begin to regrow, but this regeneration is aborted as a fibrotic scar is laid down within the wound. Reconnection of several neuronal pathways does not occur. Functional recovery from such injuries is therefore poor and morbidity severe, particularly for those patients with spinal cord damage. Although palliative measures are available to improve the quality of life, there is no accepted treatment to restore impaired sensory or motor function, so patients remain significantly and permanently debilitated. However, the rapid recent advances that have been made in our understanding of the underlying cellular and trophic pathology of such injuries offer the potential for development of novel therapies to control scarring, enhance neuron survival and stimulate axon regeneration, thereby promoting functional recovery.