Since the inception of the NHS, user charges have been present for prescription medication. However since 1968 there has been a steady increase in this charge, particularly notable during the 1980s. The main justification for user charges is their revenue raising potential, and a recent government report has backed the use of user charges for prescription drugs. Whilst there is extensive evidence of the impact of user charges on utilisation of health care in the US, few studies exist in the UK. An accurate estimation of the price elasticity of utilisation is necessary if the full consequences of user charges are to be examined. This paper uses a cointegration estimation technique to estimate the price elasticity for prescription drug utilisation in the UK.

Drug Utilization↗

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A theoretical and experimental model of ventricular interdependence.

Because of the close anatomical association between the ventricles, the volume of one ventricle can directly affect the volume and pressure within the other ventricle. To study the mechanical coupling between the ventricles, we modeled the right and left ventricles as a two-compartment model with right wall (Crw), septal (Cs), and left wall (Clw) compliances. Based on the balances of forces across the septum, four equations were obtained to predict the transfer of pressure (P) and volume (V) information from one ventricle to another. The validity of the theoretical analysis was tested first in a physical model and then in a post-mortem heart preparation. The standard errors of estimate comparing the predicted to measured values were low for both the physical model and the post-mortem heart data. All values were significantly related (P less than 0.05) with r greater than 0.89. The results show excellent correlation between predicted and measured values. This model provides a better understanding of ventricular interdependence and may help to predict effects of hypertrophy and/or myocardial ischemia on ventricular interdependence.

Animals↗

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In-vitro activity of piperacillin/tazobactam relative to other antibiotics against blood culture isolates.

Resistance of bacteria to antibiotics is an increasing problem in many countries. Accurate locally relevant information is essential for detection and control of emerging resistance and to facilitate choice of empirical antibiotic therapy in the immediate management of seriously ill patients. We have determined the minimum inhibitory concentration of piperacillin/tazobactam for 97 strains of bacteria (55 Enterobacteriaceae, 13 non-fermentative Gram-negative bacilli, 22 Staphylococcus aureus, 6 Enterococcus faecalis and 1 Bacillus cereus) isolated from blood cultures and compared its activity to that of amoxycillin, co-amoxiclav, cephalothin, cefotaxime, ceftazidime, ciprofloxacin, gentamicin, piperacillin, cefotaxime. The strains were consecutive non-fastidious isolates with the following qualifications: coagulase negative staphylococci and diphtheroids were excluded and the number of Staphylococcus aureus isolates was limited to 12 methicillin-resistant and 10 methicillin-sensitive strains. Multiple isolates of the same species from individual patients were not included. The minimum inhibition concentrations of methicillin, penicillin, teichoplanin and vancomycin were also determined for specific groups of organisms. MICs were determined by the Etest method (AB Biodisk, Solna, Sweden) on Mueller Hinton agar. The MICs of appropriate American Type Culture Collection control strains were determined. Based on the interpretative criteria of the National Committee for Clinical Laboratory Standards (USA), 87 per cent of Gram-negative bacilli were susceptible to piperacillin/tazobactam compared with amoxycillin 26 per cent, cephalothin 35 per cent, co-amoxiclav 54 per cent, piperacillin 56 per cent, cefotaxime 69 per cent, ceftazidime 84 per cent, gentamicin 85 per cent and ciprofloxacin 91 per cent. Of all isolates 75 per cent were sensitive to piperacillin/tazobactam, compared with amoxycillin 22 per cent, cephalothin 35 per cent, piperacillin 41 per cent, co-amoxiclav 52 per cent, cefotaxime 59 per cent, ceftazidime 60 per cent, gentamicin 74 per cent and ciprofloxacin 77 per cent. Two isolates (1 E. coli and 1 Klebsiella pneumoniae) with antibiograms consistent with the relatively new resistance phenomenon of extended spectrum beta-lactamase production were identified. The spectrum of activity of piperacillin-tazobactam for empirical antibiotic therapy is significantly greater than that of piperacillin alone and is similar to that of ciprofloxacin and gentamicin.

Anti-Bacterial Agents↗

PubMedDate not supplied

Electron microscopic observations on the development of myelin in cultures of neonatal rat cerebellum.

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Animals↗

PubMedDate not supplied

Failure to induce myelin sheath formation around artificial fibres with a note on the toxicity of polyester fibres for nervous tissue in vitrol.

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Animals↗

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Variability in staff reports of the frequency of challenging behavior.

Information was collected from 88 staff about their observations of the occurrence and frequency of challenging behaviors in 22 individuals with developmental disabilities with whom they worked. Staff reports suggested considerable variability in challenging behavior in the presence of different staff and, from day to day, in the presence of the same staff. Variability was greater for stereotyped than for aggressive/destructive behavior, and for more frequent behavior. Managers reported generally less challenging behavior than their staff. The validity of the findings was discussed and their implications for research and practice considered.

Adolescent↗

PubMedDate not supplied

Transduction and rearrangement of the myc gene by feline leukaemia virus in naturally occurring T-cell leukaemias.

Evidence of myc gene transduction by feline leukaemia virus in several spontaneous lymphoid tumours of cats suggests that recombinant viruses carrying oncogenes may be much more involved in oncogenesis in natural conditions than previously recognized.

Animals↗

PubMedDate not supplied

The hemodynamic effects of intrathecal oxytocin in normal dogs.

OBJECTIVE: To evaluate the hemodynamic effects produced by intrathecal administration of oxytocin in healthy isoflurane-anesthetized dogs. STUDY DESIGN: Prospective single-dose trial. ANIMAL POPULATION: Six healthy purpose-bred adult dogs weighing between 7.3 and 14.5 kg. METHODS: Dogs were anesthetized with isoflurane and instrumented. Oxytocin at a dosage of 1.6 microg/kg was administered intrathecally at the cisternal space at time 0. Hemodynamic data were recorded immediately before and at 1, 5, 15, 30, and 60 minutes after oxytocin administration. Statistical analysis included an analysis of variance (ANOVA) for repeated measures over time. A P < .05 was considered significant. RESULTS: Baseline values +/- standard error of the mean for heart rate, mean arterial pressure, central venous pressure, cardiac output, systemic vascular resistance, mean pulmonary arterial pressure, pulmonary arterial occlusion pressure, and pulmonary vascular resistance were 101 +/- 11 beats/minute, 76 +/- 7 mm Hg, 4 +/- 4 mm Hg, 1.9 +/- 0.7 L/min, 3834 +/- 2556 dynes x sec/cm5, 14 +/- 3 mm Hg, 4 +/- 2 mm Hg, and 430 +/- 201 dynes x sec/cm5, respectively. Variations from the baseline values were seen in all parameters after intrathecal oxytocin administration, but no statistically significant differences were found. CONCLUSION: The intrathecal injection of 1.6 microg/kg of oxytocin is associated with minimal hemodynamic effects during isoflurane anesthesia. CLINICAL RELEVANCE: This study revealed no clinically significant deleterious effects from the intrathecal administration of oxytocin, and investigations into its use as a perioperative analgesic are therefore warranted.

Analysis of Variance↗

PubMedDate not supplied

"Been to Africa".

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Attitude of Health Personnel↗

PubMedDate not supplied

tRNA-ribosome interactions.

Direct measurements of the rates of dissociation of dipeptidyl-tRNA from the ribosome show that hyperaccurate SmP and SmD ribosomes have unstable A-site binding of peptidyl-tRNA, while P-site binding is extremely stable in relation to the wild type. Error-prone Ram ribosomes, on the other hand, have stable A-site and unstable P-site binding of peptidyl-tRNA. At least for these mutant ribosomes, we conclude that stabilization of peptidyl-tRNA in one site destabilizes binding in the other. Elongation factor Tu (EF-Tu) undergoes a dramatic structural transition from its GDP-bound form to its active GTP-bound form, in which it binds aa-tRNA (aminoacyl-tRNA) in ternary complex. The effects of substitution mutations at three sites in domain I of EF-Tu, Gln124, Leu120, and Tyr160, all of which point into the domain I-domain III interface in both the GTP and GDP conformations of EF-Tu, were examined. Mutations at each position cause large reductions in aa-tRNA binding. An attractive possibility is that the mutations alter the domain I-domain III interface such that the switching of EF-Tu between different conformations is altered, decreasing the probability of aa-tRNA binding. We have previously found that two GTPs are hydrolyzed per peptide bond on EF-Tu, the implication being that two molecules of EF-Tu may interact on the ribosome to catalyze the binding of a single aa-tRNA to the A-site. More recently we found that ribosomes programmed with mRNA constructs other than poly(U), including the sequence AUGUUUACG, invariably use two GTPs per peptide bond in EF-Tu function. Other experiments measuring the protection of aa-tRNA from deacylation or from RNAse A attack show that protection requires two molecules of EF-Tu, suggesting an extended ternary complex. To remove remaining ambiguities in the interpretion of these experiments, we are making direct molecular weight determinations with neutron scattering and sedimentation-diffusion techniques.

Bacterial Proteins↗

PubMedDate not supplied

Neuritogenic-neurotoxic effects of membrane-associated forms of amyloid precursor protein.

The membrane-bound glycoprotein, amyloid precursor protein (APP), plays a central role in Alzheimer's disease (AD). The present paper investigates the neuritogenic-neurotoxic properties of this protein and relates them to possible aetiopathological mechanisms in AD. Marked differences in neuritic differentiation were detected when comparing untransfected tetraploid mouse neuroblastoma cells (or vector only cells) with transfected cells overexpressing APP(751). Transfected cells developed neurites quicker, and whereas all transfected cells differentiated, the degree of differentiation of untransfected cells was more variable. Fully differentiated transfected and untransfected cells had marked differences in neuritic morphology. Transfected cells had more neurites per cell, these being shorter and more branched than neurites on untransfected cells. The precocious differentiation of transfected cells was not maintained with neuritic process disintegration and cell death occurring from the seventh day onwards. Untransfected cells continued to extend their neuritic processes for up to five weeks. Membrane-associated forms of APP were responsible for these effects, rather than secreted APP or the beta/A4-peptide. Combined data from Western blot and immunocytochemical procedures showed a prominent accumulation of APP-C-terminal fragments in the perinuclear region, neuritic varicosities and growth cones of transfected cells, suggesting their involvement in the neuritogenic-neurotoxic process. Similar neuritogenic-neurotoxic mechanisms occurring in vivo, in association with compensatory synaptoplastic responses in the aged brain, may be part of the pathological process in AD.

Alzheimer Disease↗

PubMedDate not supplied

Screening for tuberculosis in an east London HIV clinic.

A prospective study was carried out to assess the value of routine skin tuberculin testing and chest radiography in HIV seropositive patients, attending the Genitourinary Medicine (GUM) clinic between July 1991-May 1992. 144 consecutive HIV seropositive patients had tuberculin Tine tests and chest radiographs performed. Ten patients were treated for active tuberculosis (TB) on the basis of abnormal radiography with or without strongly positive (Grade 3/4) skin tuberculin tests. A further 10 patients received prophylaxis on the basis of abnormal chest radiography consistent with previous tuberculous infection or strongly positive tuberculin tests. Active or previous tuberculous infection was found in the UK born Caucasian homosexual population as well as in injecting drug users and patients who were born in areas of high TB prevalence. Screening for TB in HIV seropositive patients is important both for detecting asymptomatic tuberculous infection and for recognizing patients at risk for reactivation of latent TB. We showed a high pick-up rate with 20 out of 144 patients having treatment as a result of screening.

Female↗

PubMedDate not supplied

Intravenous enzyme replacement therapy: better in home or hospital?

This article evaluates satisfaction with enzyme replacement therapy (ERT) at home and at hospital in adult patients with Fabry and Gaucher diseases. A questionnaire was developed and sent to 34 patients with Fabry disease who were receiving ERT with agalsidase alfa (Replagal) and to 49 patients with type I Gaucher disease who were receiving ERT with glucocerebrosidase (Cerezyme). Of the 45 returned questionnaires, 20 were from patients with Fabry disease and 25 from patients with Gaucher disease. Hospital treatment visits were reported as stressful by 18 patients (40%), whereas only 4 (9%) patients reported that home therapy was stressful. Both groups of patients adjusted well to receiving home-based therapy. Nearly all of the patients with Fabry disease (19 patients, 95%) and Gaucher disease (21 patients, 84%) preferred home-based therapy. Treatment in the home was reported as more comfortable, less stressful, more effective and had less impact on family life. Only 4 (9%) patients chose to continue receiving infusions in hospital. The majority of patients with Fabry disease and Gaucher disease found home-based therapy to be more convenient and less stressful than hospital-based therapy.

Adaptation, Psychological↗

PubMedDate not supplied

Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma.

Vascular endothelial growth factor (VEGF) is a dimeric glycosylated polypeptide growth factor with potent angiogenic, mitogenic, and vascular permeability-enhancing properties specific for endothelial cells. In humans, VEGF seems to play a major role in tumor growth, and plasma concentrations correlate with tumor burden, response to therapy, and disease progression. This study compared plasma VEGF concentrations in healthy client-owned dogs (n = 17) to dogs with hemangiosarcoma (HSA; n 16). Dogs with HSA were significantly more likely to have detectable concentrations of plasma VEGF (13/17) compared to healthy dogs (1/17; P < .001). The median plasma VEGF concentration for dogs with HSA was 17.2 pg/mL (range, < 1.0-66.7 pg/mL). Plasma VEGF concentrations in dogs with HSA did not correlate with stage of disease or tumor burden, but 1 dog had undetectable VEGF during chemotherapy that subsequently increased with disease progression.

Animals↗