Prescribing naloxone to actively injecting heroin users: a program to reduce heroin overdose deaths.

Heroin overdose deaths have increased alarmingly in Chicago over the past decade. Naloxone, an opioid antagonist with no abuse potential, has been used to reverse opiate overdose in emergency medical settings for decades. We describe here a program to educate opiate users in the prevention of opiate overdose and its reversal with intramuscular naloxone.

Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations.

Congenital myasthenic syndromes are inherited disorders of neuromuscular transmission characterized by fatigable muscle weakness. Autosomal recessive acetylcholine receptor (AChR) deficiency syndromes, in which levels of this receptor at the neuromuscular junction are severely reduced, may be caused by mutations within genes encoding the AChR or the AChR-clustering protein, rapsyn. Most patients have mutations within the rapsyn coding region and are either homozygous for N88K or heteroallelic for N88K and a second mutation.

Dok-7 mutations underlie a neuromuscular junction synaptopathy.

Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission characterized by fatigable muscle weakness. One major subgroup of patients shows a characteristic "limb girdle" pattern of muscle weakness, in which the muscles have small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function. We showed that recessive inheritance of mutations in Dok-7, which result in a defective structure of the neuromuscular junction, is a cause of CMS with proximal muscle weakness.

Effects of short-term isocapnic hyperoxia and hypoxia on cardiovascular function.

Both hypoxia and hyperoxia have major effects on cardiovascular function. However, both states affect ventilation and many previous studies have not controlled CO(2) tension. We investigated whether hemodynamic effects previously attributed to modified O(2) tension were still apparent under isocapnic conditions.

Selectivity of NSAIDs for COX-2 and cardiovascular outcome.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) with increased selectivity for the cyclooxygenase-2 (COX-2) isoform reduce gastrotoxicity but may increase adverse cardiovascular events.

Methods: We searched the literature for studies that reported the odds ratio (OR) for such events following exposure to NSAIDs.

Results: For studies comparing NSAID use with no use, increased COX-2 selectivity was significantly related to cardiovascular risk (log OR) amongst observational studies (R = -0.

Reducing variation in antibacterial prescribing rates for 'cough/cold' and sore throat between 1993 and 2001: regional analyses using the general practice research database.

Objective: To use the General Practice Research Database (GPRD) to explore the regional variation in prescribing for single diagnostic episodes of 'cough/cold' and sore throat and how this changed between 1993 and 2001.

Methods: Data from the GPRD was used to conduct a longitudinal survey of morbidity and antibiotic prescribing data.

Results: Nationally there has been a substantial reduction in diagnosed episodes per 1000 patient years at risk for both diagnoses: from 104.

Cyclin A1 is a p53-induced gene that mediates apoptosis, G2/M arrest, and mitotic catastrophe in renal, ovarian, and lung carcinoma cells.

We were the first to identify cyclin A1 as a p53-induced gene by cDNA expression profiling of p53-sensitive and -resistant tumor cells [Maxwell S. A. and Davis G.

Prediction of serum total antioxidant activity from the concentration of individual serum antioxidants.

Background: Redox mechanisms are implicated in the pathogenesis of many diseases and several assays of total antioxidant capacity (TAOC) have been reported. Large epidemiological databases contain information on individual serum antioxidants as well as disease-specific phenotypic data. However, antioxidants work co-operatively in biological systems and it is important to be able to translate individual antioxidant measures into those of global antioxidant defence.

Dietary habits of the Somali population in Liverpool, with respect to foods containing calcium and vitamin D: a cause for concern?

Background: A large percentage of Liverpool Somalis have vitamin D deficiency and low calcium excretion. The dietary habits of Liverpool Somalis were investigated with respect to food items containing calcium and vitamin D.

Methods: A questionnaire, administered by a Somali field worker, assessed the intake of food of 60 adult (45 females and 15 males; mean age 42 years) and 10 child (seven females and three males; mean age 10 years) Somali volunteers.

Failure to implement hospital antimicrobial prescribing guidelines: a comparison of two UK academic centres.

Background: Rational antimicrobial therapy should provide maximum benefit to patients while minimizing the development of resistant microorganisms.

Objectives: The aim of this study was to investigate (i) which antimicrobial drugs were chosen by hospital doctors faced with two common infections [community-acquired pneumonia (CAP) and urinary tract infection (UTI)], (ii) whether these choices were compliant with local guidance and (iii) the factors that influenced antimicrobial choice.

Methods: A questionnaire based on two hypothetical clinical scenarios was distributed to 316 hospital doctors across four UK NHS hospitals in two cities (Newcastle and Edinburgh).

Interaction of single-dose ezetimibe and steady-state cyclosporine in renal transplant patients.

This open-label, single-period study evaluated the single-dose pharmacokinetics of ezetimibe (EZE) 10 mg in the setting of steady-state cyclosporine (CyA) dosing in renal transplant patients. A single 10-mg dose of EZE was coadministered with the morning dose of CyA (75-150 mg twice a day). Total EZE (sum of unconjugated, parent EZE and EZE-glucuronide; EZE-total) AUC(0-last) and Cmax were compared to values derived from a prespecified database of healthy volunteers.

High-flux beam source for cold, slow atoms or molecules.

We demonstrate and characterize a high-flux beam source for cold, slow atoms or molecules. The desired species is vaporized using laser ablation, then cooled by thermalization in a cryogenic cell of buffer gas. The beam is formed by particles exiting a hole in the buffer gas cell.

Tick modulation of the in-vitro expression of adhesion molecules by skin-derived endothelial cells.

As a tick feeds, its saliva induces innate and acquired immune responses in the host, including leucocyte infiltration into the bite site. Tick salivary glands produce molecules, however, that counteract many host defences against blood feeding. The effects of salivary-gland extracts (SGE) of Dermacentor andersoni and Ixodes scapularis on the expression of various adhesion molecules [E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)] by the sEND.

Co-proxamol overdose is associated with a 10-fold excess mortality compared with other paracetamol combination analgesics.

Aims: To assess the relative toxicity of co-proxamol in overdose in comparison to the 2 other paracetamol-opioid combination products, co-codamol and co-dydramol.

Methods: Data collected over a 2-year period (July 2000-June 2002) was used to estimate the frequency of overdose and death for the three most popular paracetamol-opioid compound analgesics. Prescription data for Scotland and Edinburgh, the number of overdoses (derived from overdose admissions in Edinburgh) or Poisons Information Service contacts in Scotland, and national death records were used to calculate a series of indicators relating morbidity (admissions), surrogates of morbidity (poisons enquiries by telephone or internet) and mortality to prescriptions.

Midbrain dopaminergic development in vivo and in vitro from embryonic stem cells.

The midbrain dopaminergic (mDA) neurons play a key role in the function of a variety of brain systems, including motor control and reward pathways. This has led to much interest in these neurons as targets for intervention in human disorders such as Parkinson's disease and schizophrenia. A major area of interest is to direct embryonic stem (ES) cells to differentiate into mDA neurons in vitro, which can then be used for cell therapy or drug screening.

Pulse transit time measured from the ECG: an unreliable marker of beat-to-beat blood pressure.

The arterial pulse-wave transit time can be measured between the ECG R-wave and the finger pulse (rPTT), and has been shown previously to have a linear correlation with blood pressure (BP). We hypothesized that the relationship between rPTT, preejection period (PEP; the R-wave/mechanical cardiac delay), and BP would vary with different vasoactive drugs. Twelve healthy men (mean age 22 yr) were studied.

The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe.

Objective: The objective of this study was to evaluate the pharmacodynamic effects and safety of the co-administration of ezetimibe and fluvastatin in healthy hypercholesterolemic subjects at clinically-relevant doses and to evaluate the potential for a pharmacokinetic drug interaction between ezetimibe and fluvastatin.

Methods: In a single-center, evaluator-blind, placebo-controlled, multiple-dose, parallel-group study 32 healthy subjects with hypercholesterolemia were randomized to 4 treatments administered once daily for 14 days: ezetimibe 10 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe 10 mg, and ezetimibe placebo. Blood samples were collected to measure serum lipids and to determine steady-state pharmacokinetics.

Evidence based prescribing.

Is the goal, but prescribers still need education, experience, and common sense

ECG abnormalities in co-proxamol (paracetamol/dextropropoxyphene) poisoning.

Objectives: 1) To investigate ECG changes following co-proxamol (paracetamol 325 mg and dextropropoxyphene 32.5 mg) overdose in comparison to co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine) in a prospective study. 2) To examine the relationship between estimated dextropropoxyphene dose and ECG changes in a larger patient population.

Murine extramedullary erythropoiesis induced by tick infestation.

Tick saliva contains molecules that modulate the haemostasis, pain/itch responses, wound healing and immune defences of the host. Using BALB/c mice that were each infested with 10 nymphs of Dermacentor andersoni Stiles (Acari: Ixodidae), an attempt has now been made to determine the influence of tick infestation on the expression of leucocyte adhesion molecules in the host. The ticks became fully engorged by the fourth to sixth day of infestation.

Does a hospital formulary influence prescribing practice in an acute medical admissions unit?

Aim: To assess the extent to which prescribing of cardiovascular medications in a busy medical unit deviates from the local joint primary and secondary care drug formulary guidelines.

Method: A retrospective audit of the case notes, prescription charts and discharge summaries of 150 randomly selected emergency medical admissions over a 4 month period.

Results: No patient receiving a non-formulary cardiovascular drug on admission had the choice reviewed in line with formulary recommendations.