Biomedical subjects

A Giuffrida

Publications and source records attributed to A Giuffrida.

At least 37 records · Page 2Linked to original sources

PubMed2000

Reversal of dopamine D(2) receptor responses by an anandamide transport inhibitor.

We characterized the pharmacological properties of the anandamide transport inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404) in rats and investigated the effects of this drug on behavioral responses associated with activation of dopamine D(2) family receptors. Rat brain slices accumulated [(3)H]anandamide via a high-affinity transport mechanism that was blocked by AM404. When administered alone in vivo, AM404 caused a mild and slow-developing hypokinesia that was significant 60 min after intracerebroventricular injection of the drug and was reversed by the CB1 cannabinoid receptor antagonist SR141716A. AM404 produced no significant catalepsy or analgesia, two typical effects of direct-acting cannabinoid agonists. However, AM404 prevented the stereotypic yawning produced by systemic administration of a low dose of apomorphine, an effect that was dose-dependent and blocked by SR141716A. Furthermore, AM404 reduced the stimulation of motor behaviors elicited by the selective D(2) family receptor agonist quinpirole. Finally, AM404 reduced hyperactivity in juvenile spontaneously hypertensive rats, a putative model of attention deficit hyperactivity disorder. The results support a primary role of the endocannabinoid system in the regulation of psychomotor activity and point to anandamide transport as a potential target for neuropsychiatric medicines.

Animals↗

PubMed2000

Quantification of bioactive acylethanolamides in rat plasma by electrospray mass spectrometry.

We developed a high-performance liquid chromatography/mass spectrometry (HPLC/MS) method for the identification and quantification of anandamide, an endogenous cannabinoid substance, and other fatty acid ethanolamides (AEs) in biological samples. Using a mobile-phase system of methanol/water and gradient elution, we achieved satisfactory resolution of all major AEs, including anandamide, palmitylethanolamide (PEA), and oleylethanolamide (OEA). Electrospray-generated quasi-molecular species were used as diagnostic ions and detected by selected ion monitoring (SIM). Synthetic deuterium-labeled AEs were used as internal standards, and quantification was carried out by isotope dilution. A linear correlation (r2 = 0.99) was observed in the calibration curves for standard AEs over the range 0-0.5 nmol. Detection limits between 0.1 and 0.3 pmol per sample and quantification limits between 0.5 and 1.2 pmol per sample were obtained. The method was applied to the quantification of anandamide, PEA, and OEA in plasma prepared from rat blood collected either by cardiac puncture or by decapitation. After cardiac puncture, AE levels were in the low-nanomolar range: anandamide, 3.1 +/- 0.6 pmol/ml; PEA, 9.4 +/- 1.6 pmol/ml; OEA, 9.2 +/- 1.8 pmol/ml (mean +/- SE, n = 9). By contrast, after decapitation AEs were dramatically elevated (anandamide, 144 +/- 13 pmol/ml; PEA, 255 +/- 55 pmol/ml; OEA, 175 +/- 48 pmol/ml). Thus, disruptive procedures of blood collection may result in gross overestimates in the concentrations of circulating AEs.

Amides↗

PubMed2000

Target payments in primary care: effects on professional practice and health care outcomes.

BACKGROUND: The method by which physicians are paid may affect their professional practice. Although payment systems may be used to achieve policy objectives (e.g. improving quality of care, cost containment and recruitment to under-served areas), little is known about the effects of different payment systems in achieving these objectives. Target payments are a payment system which remunerate professionals only if they provide a minimum level of care. OBJECTIVES: To evaluate the impact of target payments on the professional practice of primary care physicians (PCPs) and health care outcomes. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register; the Cochrane Controlled Trials Register; MEDLINE (1966 to October 1997); BIDS EMBASE (1980 to October 1997); BIDS ISI (1981 to October 1997); EconLit (1969 to October 1997); HealthStar (1975 to October 1997) Helmis (1984 to October 1997); health economics discussion paper series of the Universities of York, Aberdeen, Sheffield, Bristol, Brunel, and McMaster; Swedish Institute of Health Economics; RAND corporation; and reference lists of articles. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series analyses of interventions comparing the impact of target payments to primary care professionals with alternative methods of payment, on patient outcomes, health services utilisation, health care costs, equity of care, and PCP satisfaction with working environment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Two studies were included involving 149 practices. The use of target payments in the remuneration of PCPs was associated with improvements in immunisation rates, but the increase was statistically significant in only one of the two studies. REVIEWER'S CONCLUSIONS: The evidence from the studies identified in this review is not of sufficient quality or power to obtain a clear answer to the question as to whether target payment remuneration provides a method of improving primary health care. Additional efforts should be directed in evaluating changes in physicians' remuneration systems. Although it would not be difficult to design a randomised controlled trial to evaluate the impact of such payment systems, it would be difficult politically to conduct such trials.

Humans↗

PubMed2000

Capitation, salary, fee-for-service and mixed systems of payment: effects on the behaviour of primary care physicians.

BACKGROUND: It is widely believed that the method of payment of physicians may affect their clinical behaviour. Although payment systems may be used to achieve policy objectives (e.g. cost containment or improved quality of care), little is known about the effects of different payment systems in achieving these objectives. OBJECTIVES: To evaluate the impact of different methods of payment (capitation, salary, fee for service and mixed systems of payment) on the clinical behaviour of primary care physicians (PCPs). SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register; the Cochrane Controlled Trials Register; MEDLINE (1966 to October 1997); BIDS EMBASE (1980 to October 1997); BIDS ISI (1981 to October 1997); EconLit (1969 to October 1997); HealthStar (1975 to October 1997) Helmis (1984 to October 1997); health economics discussion paper series of the Universities of York, Aberdeen, Sheffield, Bristol, Brunel, and McMaster; Swedish Institute of Health Economics; RAND corporation; and reference lists of articles. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series analyses of interventions comparing the impact of capitation, salary, fee for service (FFS) and mixed systems of payment on primary care physician satisfaction with working environment; cost and quantity of care; type and pattern of care; equity of care; and patient health status and satisfaction. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Four studies were included involving 640 primary care physicians and more than 6400 patients. There was considerable variation in study setting and the range of outcomes measured. FFS resulted in more primary care visits/contacts, visits to specialists and diagnostic and curative services but fewer hospital referrals and repeat prescriptions compared with capitation. Compliance with a recommended number of visits was higher under FFS compared with capitation payment. FFS resulted in more patient visits, greater continuity of care, higher compliance with a recommended number of visits, but patients were less satisfied with access to their physician compared with salaried payment. REVIEWER'S CONCLUSIONS: It is noteworthy that so few studies met the inclusion criteria. There is some evidence to suggest that the method of payment of primary care physicians affects their behaviour, but the findings' generalisability is unknown. More evaluations of the effect of payment systems on PCP behaviour are needed, especially in terms of the relative impact of salary versus capitation payments.

Capitation Fee↗

PubMed2000

The endocannabinoid system: a physiological perspective on its role in psychomotor control.

The discovery of cannabinoid receptors has led to the identification of two natural activators for these receptors, anandamide and 2-arachidonoylglycerol, and to the elucidation of their biochemical pathways of formation and inactivation. Although the physiological significance of the endogenous cannabinoid system is still poorly understood, important information is becoming available on the possible functional roles of this system in the basal ganglia, a forebrain region that is involved in the control of sensorimotor and motivational aspects of behavior. These discoveries - which are going to enrich the way in which we look at basal ganglia functions - are summarized in this mini-review. The role of the endocannabinoids as modulators of psychomotor behaviors and the potential therapeutic perspectives deriving from the pharmacological manipulation of the endogenous cannabinoid system are also discussed.

Animals↗

PubMed2000

Endogenous cannabinoid signaling and psychomotor disorders.

The effects of cannabinoids on motor behaviors and cognitive functions are well documented. The discovery of the CB1 cannabinoid receptor and the mapping of its distribution in the central nervous system have provided a rationale to elucidate the molecular and cellular mechanisms of cannabinoid actions. The identification of naturally occurring ligands for these receptors, anandamide and 2-arachidonylglycerol, has prompted a large research effort aimed at investigating the physiological role of the endogenous cannabinoid system, as well as its potential use as a target for novel therapeutic interventions. This mini-review discusses the participation of the endogenous cannabinoid system in the regulation of motor behaviors, pointing out its possible involvement in the pathophysiology of psychomotor disorders.

Animals↗

PubMed2000

The endocannabinoid system as a target for therapeutic drugs.

Cannabinoid receptors, the molecular targets of the cannabis constituent Delta9-tetrahydrocannabinol, are present throughout the body and are normally bound by a family of endogenous lipids - the endocannabinoids. Release of endocannabinoids is stimulated in a receptor-dependent manner by neurotransmitters and requires the enzymatic cleavage of phospholipid precursors present in the membranes of neurons and other cells. Once released, the endocannabinoids activate cannabinoid receptors on nearby cells and are rapidly inactivated by transport and subsequent enzymatic hydrolysis. These compounds might act near their site of synthesis to serve a variety of regulatory functions, some of which are now beginning to be understood. Recent advances in the biochemistry and pharmacology of the endocannabinoid system in relation to the opportunities that this system offers for the development of novel therapeutic agents will be discussed.

Animals↗

PubMed2000

Efficiency and administrative costs in primary care.

We use a formal model to examine the implications of endogenous managerial effort for the interpretation and estimation of efficiency in health care organisations. The model is applied to investigate the doubling of the cost of administering primary care in England in real terms between 1989/1990 and 1994/1995. The main cost determinant was the number of general practitioners (GPs), and there were economies of scale but not of scope. Fund-holding had a positive but small effect on administrative costs, so that the recent abolition of fund-holding may do little to reduce primary care administrative costs. After allowing for changes in the numbers of primary care practitioners, the quality of primary care and the extent of fund-holding, most of the increase in costs was unexplained, and may reflect additional but unmeasured increases in the administrative burden associated with the 1990 reforms. There was little variation in relative efficiency across areas.

Cost Allocation↗

PubMed1999

Measuring quality of care with routine data: avoiding confusion between performance indicators and health outcomes.

OBJECTIVE: To investigate the impact of factors outside the control of primary care on performance indicators proposed as measures of the quality of primary care. DESIGN: Multiple regression analysis relating admission rates standardised for age and sex for asthma, diabetes, and epilepsy to socioeconomic population characteristics and to the supply of secondary care resources. SETTING: 90 family health services authorities in England, 1989-90 to 1994-5. RESULTS: At health authority level socioeconomic characteristics, health status, and secondary care supply factors explained 45% of the variation in admission rates for asthma, 33% for diabetes, and 55% for epilepsy. When health authorities were ranked, only four of the 10 with the highest age-sex standardised admission rates for asthma in 1994-5 remained in the top 10 when allowance was made for socioeconomic characteristics, health status, and secondary care supply factors. There was also substantial year to year variation in the rates. CONCLUSION: Health outcomes should relate to crude rates of adverse events in the population. These give the best indication of the size of a health problem. Performance indicators, however, should relate to those aspects of care which can be altered by the staff whose performance is being measured.

Age Distribution↗

PubMed1999

Elevated endogenous cannabinoids in schizophrenia.

Evidence suggests that cannabinoid receptors, the pharmacologcial target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia. To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal fluid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were purified from cerebrospinal fluid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quantified by isotope dilution gas-chromatography/mass-spectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than non-schizophrenic controls (p < 0.05). By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups. The findings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.

Adult↗

PubMed1999

The use of citalopram in an integrated approach to the treatment of eating disorders: an open study.

This study investigated the efficacy and safety of citalopram in the treatment of eating disorders. Eighteen female patients gave their informed consent to enrollment in the trial: twelve with bulimia nervosa, six with anorexia nervosa according to the DSM IV criteria. They received individual systemic psychotherapy and took 20 mg/day citalopram for 8 weeks. At the beginning and end of the trial, their BMI, body fat and lean mass were checked and they completed the Eating Disorder Inventory and Binge Scale. The results showed that citalopram is effective and safe in the treatment of eating disorders: binge eating episodes and mean scores in three EDI subscales (bulimia, ineffectiveness and interoceptive awareness) significantly decreased in the bulimic patients, and mean scores in the EDI body dissatisfaction subscale significantly decreased in the anorexic patients.

Adolescent↗

PubMed1999

Productivity and efficiency changes in primary care: a Malmquist index approach.

The reforms of the National Health System in the UK introduced in 1990 led to substantial changes in the organisation of primary health care. In this paper we analyse the efficiency of primary care provision in the English Family Health Service Authorities (FHSAs) over the period 1990/91-1994/95. We use Data Envelopment Analysis to measure Malmquist indices of productivity changes, which are then decomposed into indices of pure technical efficiency change, scale efficiency change and technological change. The analysis indicates a small improvement in the productivity over the period considered. The increase is attributed to pure technical efficiency improvement and positive change in scale efficiency, while the technology does not show significant change. The analysis suggests that there is very limited scope for productivity gains in this sector.

Data Interpretation, Statistical↗

PubMed1999

Dopamine activation of endogenous cannabinoid signaling in dorsal striatum.

We measured endogenous cannabinoid release in dorsal striatum of freely moving rats by microdialysis and gas chromatography/mass spectrometry. Neural activity stimulated the release of anandamide, but not of other endogenous cannabinoids such as 2-arachidonylglycerol. Moreover, anandamide release was increased eightfold over baseline after local administration of the D2-like (D2, D3, D4) dopamine receptor agonist quinpirole, a response that was prevented by the D2-like receptor antagonist raclopride. Administration of the D1-like (D1, D5) receptor agonist SKF38393 had no such effect. These results suggest that functional interactions between endocannabinoid and dopaminergic systems may contribute to striatal signaling. In agreement with this hypothesis, pretreatment with the cannabinoid antagonist SR141716A enhanced the stimulation of motor behavior elicited by systemic administration of quinpirole. The endocannabinoid system therefore may act as an inhibitory feedback mechanism countering dopamine-induced facilitation of motor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1999

Migration of mesothelioma cells correlates with histotype-specific synthesis of extracellular matrix.

Three human pleural malignant mesothelioma cell cultures (MM) of epithelioid (E1), fibrous (F1) and byphasic (B1) histotype were studied in their synthesis of the extracellular matrix (ECM) components laminin (LM), fibronectin (FN), type IV collagen (cIV), and in their chemotactic and haptotactic migration towards the ECM produced proteins. MM-B1 showed the highest FN synthesis and release; MM-E1 produced the highest quantity of basement membrane constituents LM and cIV; MM-F1 weakly produced and released FN, LM and cIV. MM-B1 had the highest chemotactic and haptotactic motility, MM-F1 migrated toward the lowest concentration of LM while had reduced chemotactic activity toward FN and cIV; MM-E1 had the lowest migratory activity toward each ECM substrate. We demonstrated that three MM of different histotype are characterized by different ECM production and that these differences determine a variable ability of each MM to spread and migrate towards ECM substrates.

Cell Movement↗

PubMed1999

Modulation of integrin expression on mesotheliomas: the role of different histotypes in invasiveness.

The in vitro and in vivo integrin expression in human pleural malignant mesothelioma (MM) of three different histotypes was studied. Cell lines from MM of epithelioid (E1), fibrous (F1), byphasic histotype (B1) and normal mesothelial cells (NM) were analysed for the surface expression of alpha2, alpha3, alpha4, alpha5, alpha6, alphav, beta1, beta3, beta4 subunits and alphavbeta5 integrins. We found that alpha6, beta4 subunits and alphavbeta5, weakly detectable on NM cells, were expressed on MM cells. The beta3 subunit, well expressed on NM cells, was absent on MM cells. Differential expression among histotypes was observed, the MM-E1 was the least and the MM-B1 the most positive. Specimens for each MM histotype, were analysed by immunohistochemistry. The alpha6 and alphav subunits were more evident on the epithelioid histotype. Intense staining for beta3 and beta4 subunits, was found in all MM, particularly in invading cells, while the alpha5, and alphavbeta5 integrins were variously expressed. The different histotypes can affect the in vitro integrin expression and may indicate a preferential involvement of some subunits in vivo during MM tumor progression.

Humans↗

PubMed1998

Control of pain initiation by endogenous cannabinoids.

The potent analgesic effects of cannabis-like drugs and the presence of CB1-type cannabinoid receptors in pain-processing areas of the brain and spinal cord indicate that endogenous cannabinoids such as anandamide may contribute to the control of pain transmission within the central nervous system (CNS). Here we show that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS. Palmitylethanolamide (PEA), which is released together with anandamide from a common phospholipid precursor, exerts a similar effect by activating peripheral CB2-like receptors. When administered together, the two compounds act synergistically, reducing pain responses 100-fold more potently than does each compound alone. Gas-chromatography/mass-spectrometry measurements indicate that the levels of anandamide and PEA in the skin are enough to cause a tonic activation of local cannabinoid receptors. In agreement with this possibility, the CB1 antagonist SR141716A and the CB2 antagonist SR144528 prolong and enhance the pain behaviour produced by tissue damage. These results indicate that peripheral CB1-like and CB2-like receptors participate in the intrinsic control of pain initiation and that locally generated anandamide and PEA may mediate this effect.

Amides↗

PubMed1998

Prevalence of Mytilicola intestinalis (Copepoda: Mytilicolidae) and Urastoma cyprinae (Turbellaria: Hypotrichinidae) in marketable mussels Mytilus galloprovincialis in Italy.

Marketable mussels Mytilus galloprovincialis traded with commercial certification from production sites in Italy and abroad (France, Spain) were examined for the presence of Mytilicola intestinalis (Copepoda: Mytilicolidae) and Urastoma cyprinae (Turbellaria: Hypotrichinidae) from October 1994 to February 1996. The prevalence of M. intestinalis was 4.1% and 4.7% respectively in mussels from Lerici (La Spezia) and S. Pietro in Volta (Venice), whereas it rose to 57.9% in the samples from Spain. M. intestinalis was absent in mussels from Chioggia (Venice), Ganzirri (Messina), Taranto, Trieste and France. The prevalence of U. cyprinae varied considerably, ranging from 0.3% in mussels from Trani (Bari) to 33.2% and 86.3% respectively in those from Chioggia and Trieste. It was 85.7% in samples from France and 63.7% in those from Spain.

Animals↗

PubMed1998

Isotope dilution GC/MS determination of anandamide and other fatty acylethanolamides in rat blood plasma.

Anandamide and allied fatty acylethanolamides (AEs) may act as signalling molecules in brain and peripheral tissues. In the present study, we describe an electron-impact gas chromatography/mass spectrometry (GC/MS) method based on isotope dilution, which may be used for the identification and quantification of anandamide and other AEs in biological matrices. The calibration curves for standard AEs were linear over the range 0-1000 pmol (r2 = 0.99) with a coefficient of variation of 4% at 2.5 pmol. Detection and quantification limits were in the high fmol to low pmol range for all AEs. Using this method we measured nanomolar concentrations of three endogenous AEs in deproteinated rat blood plasma (anandamide: 5.2 pmol/ml; palmitylethanolamide: 16.7 pmol/ml; oleylethanolamide: 8.1 pmol/ml). These results are consistent with a regulatory role of anandamide and other AEs in peripheral tissues.

Amides↗