Biomedical subjects

D Baker

Publications and source records attributed to D Baker.

At least 19 recordsLinked to original sources

PubMed2007

Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors.

BACKGROUND AND PURPOSE: There is increasing evidence to suggest that cannabis can ameliorate muscle-spasticity in multiple sclerosis, as was objectively shown in experimental autoimmune encephalomyelitis models. The purpose of this study was to investigate further the involvement of CB1 and CB2)cannabinoid receptors in the control of experimental spasticity. EXPERIMENTAL APPROACH: Spasticity was induced in wildtype and CB1-deficient mice following the development of relapsing, experimental autoimmune encephalomyelitis. Spastic-hindlimb stiffness was measured by the resistance to flexion against a strain gauge following the administration of CB1 and CB2 agonists. KEY RESULTS: As previously suggested, some CB2-selective agonists (RWJ400065) could inhibit spasticity. Importantly, however, the anti-spastic activity of RWJ400065 and the therapeutic effect of non-selective CB1/CB2 agonists (R(+)WIN55,212-2 and CP55, 940) was lost in spastic, CB1-deficit mice. CONCLUSIONS AND IMPLICATIONS: The CB1 receptor controls spasticity and cross-reactivity to this receptor appears to account for the therapeutic action of some CB2 agonists. As cannabinoid-induced psychoactivity is also mediated by the CB1 receptor, it will be difficult to truly dissociate the therapeutic effects from the well-known, adverse effects of cannabinoids when using cannabis as a medicine. The lack of knowledge on the true diversity of the cannabinoid system coupled with the lack of total specificity of current cannabinoid reagents makes interpretation of in vivo results difficult, if using a purely pharmacological approach. Gene knockout technology provides an important tool in target validation and indicates that the CB1 receptor is the main cannabinoid target for an anti-spastic effect.

Animals↗

PubMed2006

The use and performance of BioSand filters in the Artibonite Valley of Haiti: a field study of 107 households.

INTRODUCTION: Approximately one billion people world-wide lack access to adequate amounts of safe water. Most are in developing countries, especially in rapidly expanding urban fringes, poor rural areas, and indigenous communities. METHODS: In February and March 2005, a field study of 107 households was conducted to evaluate the use and performance of the Manz BioSand filter in the Artibonite Valley of Haiti. Approximately 2000 filters had been installed in this area over the preceding 5 years by the staff in Community Development at Hospital Albert Schweitzer, Deschappelle, Haiti. Interviews, observations, and water samplings were carried-out by two teams of Haitian enumerators, each consisting of a nurse and a filter technician. Water analyses were performed by Haitian lab technicians using the membrane filtration method to determine Escherichia coli counts. The enumerators and the lab technicians completed a 2 week training program before beginning the study; they worked under the direct supervision of the primary investigator. Laboratory quality was monitored by running 10% blank and 10% duplicate samples. RESULTS: The households contained an average of 5.4 persons. Filters had been in use for an average of 2.5 years, and participants were generally satisfied with their filter's performance. Shallow, hand-dug wells provided the only source of water for 61% of the households, with 26% using water piped from springs or deep wells, and 13% having access to both. Only 3% had plumbing in their homes. Source water from shallow wells contained an average of 234 E. coli cfu/100 mL. Piped sources averaged 195 E. coli cfu/100 mL. Of the source water samples 26% contained 0-10 E. coli cfu/100 mL. Of the filtered water samples 97% contained 0-10 E. coli cfu/100 mL (80% with 0 cfu/100 mL, and 17% with 1-10 cfu/100 mL). Overall bacterial removal efficiency for the filters was calculated to be 98.5%. Turbidity decreased from an average of 6.2 NTU in source water samples to 0.9 NTU in the filtered water. None of the households treated the water after filtering; 91% used the filtered water only for drinking. No problems related to filter construction were observed; 13% were found to have significantly decreased flow rates (all restored by cleaning the filter). Recontamination was found to occur, with only 3% of the samples from the filters' spouts containing >10 E. coli cfu/100 mL and 22% of the stored filtered water samples at point-of-use containing >10 cfu/100 mL. CONCLUSION: The Manz BioSand filters are an attractive option for supplying water treatment to family units in rural areas of poorly developed countries.

Developing Countries↗

PubMed2006

Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain.

Cannabinoid type 1 receptors and transient receptor potential vanilloid type 1 channels have been proposed to act as metabotropic and ionotropic receptors, respectively, for two classes of endogenous polyunsaturated fatty acid amides, the acylethanolamides and the acyldopamides. Furthermore, we and others have shown that functional crosstalk occurs between these two receptors when they are expressed in the same cell. Although demonstrated in sensory neurons of the dorsal root ganglia, spinal cord and myenteric neurons, co-expression of cannabinoid type 1 and transient receptor potential vanilloid type 1 has not yet been studied in the brain. In the present study, we addressed this issue by using commercially available specific antibodies whose specificity was confirmed by data obtained with brains from cannabinoid type 1(-/-) and transient receptor potential vanilloid type 1(-/-) mice. Double cannabinoid type 1/transient receptor potential vanilloid type 1 immunofluorescence and single cannabinoid type 1 or transient receptor potential vanilloid type 1 avidin-biotin complex immunohistochemistry techniques were performed and both methods used point to the same results. Cannabinoid type 1/transient receptor potential vanilloid type 1 expression was observed in the hippocampus, basal ganglia, thalamus, hypothalamus, cerebral peduncle, pontine nuclei, periaqueductal gray matter, cerebellar cortex and dentate cerebellar nucleus. In particular, in the hippocampus, cannabinoid type 1/transient receptor potential vanilloid type 1 expression was detected on cell bodies of many pyramidal neurons throughout the CA1-CA3 subfields and in the molecular layer of dentate gyrus. In the cerebellar cortex, expression of cannabinoid type 1/transient receptor potential vanilloid type 1 receptors was found surrounding soma and axons of the vast majority of Purkinje cell bodies, whose cytoplasm was found unstained for both receptors. Cannabinoid type 1 and transient receptor potential vanilloid type 1 immunoreactivity was also detected in: a) the globus pallidus and substantia nigra, in which some intensely transient receptor potential vanilloid type 1 immunopositive cell bodies were found in dense and fine cannabinoid type 1/transient receptor potential vanilloid type 1 positive and cannabinoid type 1 positive nerve fiber meshworks, respectively; b) the cytoplasm of thalamic and hypothalamic neurons; and c) some neurons of the ventral periaqueductal gray. These data support the hypothesis of a functional relationship between the two receptor types in the CNS.

Animals↗

PubMed2005

Randomized, placebo-controlled, phase I/IIa evaluation of the safety and immunogenicity of fowlpox virus expressing HIV gag-pol and interferon-gamma in HIV-1 infected subjects.

We conducted a randomized, placebo-controlled double-blind trial to examine the safety and immunogenicity of a candidate HIV therapeutic vaccine based upon a recombinant fowl pox virus capable of coexpressing the human cytokine interferon-gamma and/or genes from HIV-1. Thirty-five eligible subjects were randomized (12 placebo, 11 fowlpox + HIV genes, 12 fowl pox + HIV genes + interferon gamma). All but one subject (placebo group) received three immunizations (by intramuscular injection on day 0, week 4 and week 12) and all completed 52 weeks of follow-up. All subjects continued to take combination antiretroviral therapy for the duration of study. There were no significant toxicity or safety concerns and the distribution of adverse events and their severity was consistent across each randomly assigned vaccine group. Comparison of placebo recipients with the combined recipients of the two vaccine constructs, in terms of anti-HIV gag ELISpot or lymphoproliferative responses, tended to favour the placebo group, but were not significantly different (difference in time-weighted mean change from baseline = 56 Spot forming units (sfu)/10(6) PBMC; p = 0.062 and 4.4 SI; p = 0.337). There were no significant changes in CTL responses by standard Cr(51) release assay. Anti-FPV antibodies were detected by week 14 in 0 placebo and 20 (87%) vaccine recipients. Although safe, neither vaccine construct appeared to possess detectable T-cell mediated anti-HIV immunogenic properties in HIV infected individuals, as measured by standard T cell assays.

AIDS Vaccines↗

PubMed2005

Dynamic creep and mechanical characteristics of SmartSet GHV bone cement.

The restrained dynamic creep behaviour and mechanical properties of SmartSet GHV bone cement have been investigated at both room temperature and body temperature. It was found that the bone cement behaves significant differently at room temperature from that at body temperature. The test temperature had a strong effect on the creep performance of the bone cements with a higher creep rate observed at body temperature at each loading cycle. For both temperatures, two stages of creep were identified with a higher creep rate during early cycling followed by a steady state creep rate. The relationship between creep deformation and loading cycle can be expressed by a Hyperb 1 model. As a visco-elastic material, the sensitivity of bone cement to the temperature change was evident during mechanical testing. Compared to the mechanical strength at room temperature, a decreased value was demonstrated at body temperature. The bending modulus was very sensitive to the change in testing temperature, where a reduction of 52% was recorded. A significant reduction in compressive and bending strength, 31 and 23% were recorded respectively. The effect of temperature on bending strength was less apparent, where only 13% reduction was exhibited at body temperature compared to room temperature.

Bone Cements↗

PubMed2005

A review of methods currently used for assessment of in vivo endothelial function.

An intact vascular endothelium is critical to the maintenance of normal arterial tone and coagulation status. Endothelial injury leading to dysfunction is thought to be a precursor to most if not all vascular disease, and has been implicated as a critical event in atherosclerosis. At present there are several methods available for detection of in vivo endothelial function, and the aim of this study was to critically review these methods. Five distinct methods were identified and studied in detail. These methods are diverse and each assesses a different vascular bed. Importantly there is no uniformity among investigators over choice of method and protocol, making it difficult to compare in vivo enothelial dysfunction between groups. These issues need to be addressed in large scale comparative analyses so that investigators can agree a common approach to endothelial function assessment.

Brachial Artery↗

PubMed2005

Cannabinoid-receptor 1 null mice are susceptible to neurofilament damage and caspase 3 activation.

Administered cannabinoids have been shown to ameliorate signs of CNS inflammatory disease in a number of animal models, including allergic encephalomyelitis. More recently, neuroprotective actions have been attributed to activation of the cannabinoid 1 receptor in a number of in vitro and in vivo models. One of these, chronic relapsing experimental allergic encephalomyelitis, is considered a robust analog of multiple sclerosis. In this study, spinal cord tissue from cannabinoid receptor 1 knockout mice was analyzed for neurofilament H and myelin basic protein content, as markers of neurons/axons and myelin respectively, during the course of chronic relapsing experimental allergic encephalomyelitis. Dephosphorylation of a neurofilament H epitope, immunoreactive to the SMI32 antibody, was assessed as a marker of axonal damage and levels of the endpoint cell death mediator caspase 3 were evaluated. It was found that both neurofilament and myelin basic protein levels decrease over the course of disease, indicating concomitant neuronal/axonal loss and demyelination. Loss of each marker was more severe in cannabinoid receptor 1 knockout animals. Increased SMI32 reactivity was observed as disease progressed. SMI32 reactivity was significantly increased in knockout animals over wildtype counterparts, an indication of greater axonal dephosphorylation and injury. Active caspase 3 levels were increased in all animals during disease, with knockout animals displaying highest levels, even in knockout animals prior to disease induction. These results indicate that lack of the cannabinoid receptor 1 is associated with increased caspase activation and greater loss and/or compromise of myelin and axonal/neuronal proteins. The increase of caspase 3 in knockout mice prior to disease induction indicates a latent physiological effect of the missing receptor. The data presented further strengthen the hypothesis of neuroprotection elicited via cannabinoid receptor 1 signaling.

Animals↗

PubMed2005

Antipsychotic depot medication and attitudes of community psychiatric nurses.

Utilization of long-acting antipsychotic injections (depots) shows wide regional variation. In many countries, community psychiatric nurses (CPNs) administer depots but their concerns and attitudes regarding these drugs are seldom considered. We aimed to investigate attitudes and knowledge towards depots in a cross-sectional survey of CPNs in London, and compare them with those of psychiatrists obtained in a previous study. Three subscales of a depot attitude/knowledge questionnaire were used with additional items which referred to aspects of the CPN role. Participants were 70 CPNs who attended an academic meeting. Most CPNs reported that they were involved in treatment decisions (78%) although some CPNs seldom asked their patients about side effects (19%) and felt that they did not have sufficient time for consultations (23%) or training (23%). Several CPNs believed that depots are old fashioned (34%) and stigmatizing (44%). Compared to psychiatrists, CPNs believed more that depots compromised patient autonomy (28%, P = 0.003) and were coercive (42%, P < 0.001). Familiarity with depots and their knowledge of side effects were positively associated with favourable attitudes. CPNs have several strongly endorsed attitudes towards depot medication. Interprofessional group differences also exist which may undermine the treatment process. Training/refresher courses about depots should highlight systematic treatment decision-making and side effect monitoring which, in turn, may improve professionals' attitudes, knowledge and clinical monitoring of depots.

Antipsychotic Agents↗

PubMed2004

Association between baseline radiographic damage and improvement in physical function after treatment of patients with rheumatoid arthritis.

OBJECTIVES: To identify factors associated with poor physical function in rheumatoid arthritis and to assess whether baseline joint damage has an impact on improvement in physical function during infliximab treatment. METHODS: 428 patients with active rheumatoid arthritis despite methotrexate treatment received methotrexate alone or with infliximab (3 mg/kg or 10 mg/kg every four or eight weeks) for 54 weeks (the ATTRACT trial). Data on clinical outcomes and physical function (assessed by the health assessment questionnaire (HAQ)) were collected. Structural damage was assessed using the van der Heijde modification of the Sharp score. Odds ratios (OR) for factors associated with severe functional disability (HAQ > or =2.0) at baseline were estimated using multiple logistic regression analyses, and baseline factors related to the change in physical function after treatment at week 54 were determined. RESULTS: Baseline radiographic scores were correlated with baseline HAQ scores. After adjustment for demographic characteristics in the logistic regression model, baseline disease activity scores, radiological joint damage, fatigue, and morning stiffness were found to be associated with severe functional disability (HAQ >2.0), with OR values of 2.00 (1.53 to 2.63), 1.82 (1.15 to 2.87), 1.19 (1.05 to 1.34), and 1.07 (1.01 to 1.13), respectively. In multiple linear regression analysis, physical disability, joint damage, and fatigue at baseline were correlated with less improvement in physical function after treatment. Infliximab treatment was associated with greater improvement in physical function. CONCLUSIONS: Greater joint damage at baseline was associated with poorer physical function at baseline and less improvement in physical function after treatment, underlining the importance of early intervention to slow the progression of joint destruction.

Antibodies, Monoclonal↗

PubMed2004

Quantitative measurement of the stresses induced during polymerisation of bone cement.

When bone cement cures, residual stresses due to bulk and thermal shrinkage will result. Present finite element (FE) simulations of implanted constructs often do not account for these stresses as an initial condition; this may lead to overestimations of the fatigue life of the cement. In the present study, an instrumented stem equipped with strain gauges and a thermocouple was employed to experimentally quantify the residual stresses induced as a result of bone cement curing within a simulated bone/cement/stem construct. Residual stresses as high as 10 MPa were observed in the cement mantle. Residual stresses of this magnitude are potentially high enough to initiate damage within the cement mantle or at the stem/cement interface immediately post-implantation. The acoustic emission technique has demonstrated that cracking and sliding mechanisms are occurring during curing, resulting in partial relaxation of these stresses. The implications for FE simulations of the implanted construct are discussed.

Bone Cements↗

PubMed2004

Carbon fibre plates in the treatment of femoral periprosthetic fractures.

A retrospective review of fractures occurring around the femoral component of total hip replacements was performed using patient notes and X rays. Between 1996 and 2002, 12 patients with total hip replacement had fixation of their periprosthetic femoral shaft fracture with carbon fibre plates. The mean patient age was 76 years (range 57-94). With regard to fracture type (Johansson Classification), three were Type 2 and nine were Type 3. In 11 cases the average time to union was 4 months (range 3-6). There was one non-union leading to implant failure. This was subsequently treated with a revision arthroplasty. There were no other significant complications. Although designed to fit the supracondylar region of the femur, we had no difficulty in applying the plate over the trochanteric region. Our results indicate that carbon fibre plates are effective in the management of femoral periprosthetic fractures in the elderly and this may be related to the unique properties of the plate.

Aged↗

PubMed2004

Hemophilia therapy innovation: development of an advanced category recombinant factor VIII by a plasma/albumin-free method. Proceedings of a Special Symposium at the XIXth Congress of the International Society on Thrombosis and Haemostasis, July 12-18, 2003, Birmingham, UK.

Replacement therapy for hemophilia A has evolved from the early use of whole blood, citrated plasma, and cryoprecipitate, to purified factor VIII (FVIII) concentrates, first derived from plasma, then produced by recombinant DNA technology. Recombinant FVIII (rFVIII) concentrates have provided improved safety for patients with hemophilia A since they significantly reduce the risk of transmission of blood-borne infections. Nevertheless, human- or animal-derived plasma proteins are still included at some step in preparation of all previously licensed rFVIII, thereby introducing the potential for transmission of human or animal pathogens. Anti-hemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM), a novel advanced category rFVIII produced without the addition of human or animal plasma proteins, has been developed with the goal of providing the greatest possible margin of safety to hemophilia patients. This report, based on a symposium of the XIXth International Society on Thrombosis and Haemostasis Congress, provides an overview of the rAHF-PFM development program as well as current findings from the global clinical evaluation of rAHF-PFM in pediatric and adult previously treated patients.

Adult↗

PubMed2004

Measuring empathy: reliability and validity of the Empathy Quotient.

BACKGROUND: Empathy plays a key role in social understanding, but its empirical measurement has proved difficult. The Empathy Quotient (EQ) is a self-report scale designed to do just that. This series of four studies examined the reliability and validity of the EQ and determined its factor structure. METHOD: In Study 1, 53 people completed the EQ, Social Desirability Scale (SDS) and a non-verbal mental state inference test, the Eyes Task. In Study 2, a principal components analysis (PCA) was conducted on data from 110 healthy individuals and 62 people reporting depersonalisation (DPD). Approximately 1 year later, Study 3, involved the re-administration of the EQ (n = 24) along with the Interpersonal Reactivity Index (IRI; n = 28). In the last study, the EQ scores of those with DPD, a condition that includes a subjective lack of empathy, were examined in depth. RESULTS: An association was found between the Eyes task and EQ, and only three EQ items correlated with the SDS. PCA revealed three factors: (1) 'cognitive empathy'; (2) 'emotional reactivity', and (3) 'social skills'. Test-retest reliability was good and moderate associations were found between the EQ and IRI subscales, suggesting concurrent validity. People with DPD did not show a global empathy deficit, but reported less social competence. CONCLUSIONS: The EQ is a valid, reliable scale and the different subscales may have clinical applications.

Adult↗

PubMed2004

Prescribing patterns in high-need Health Authority populations: how does an ethnically mixed composition affect volume and cost?

BACKGROUND: Prescribing is the most common therapeutic intervention in primary care, and there is substantial variation in prescribing practice across England. We investigate broad patterns of prescribing across Health Authorities in England, concentrating on ethnically diverse populations. METHODS: Initially we examined the association between a number of prescribing indicators from the Prescribing Support Unit Prescribing Toolkit and 'Needs Profiles'. We then considered whether the observed patterns of prescribing were appropriate, that is, could be largely explained by variations in the prevalence of a medical condition for which the corresponding group of drugs would be prescribed. RESULTS: The volume and cost of prescribing was generally lower in more ethnically diverse Health Authority populations when compared with more elderly or deprived populations. There was a significant negative association between ethnic composition and net-ingredient-cost per patient of cardiovascular drugs, but this disappeared upon adjusting for mortality from coronary heart disease. CONCLUSIONS: The volume and cost of prescribing was generally lower in more ethnically diverse Health Authority populations relative to other high-need population profiles. Further work on this subject matter is merited, particularly if individual level data is available.

Age Factors↗

PubMed2003

Quantification of neurodegeneration by measurement of brain-specific proteins.

Quantification of neurodegeneration in animal models is typically assessed by time-consuming and observer-dependent immunocytochemistry. This study aimed to investigate if newly developed ELISA techniques could provide an observer-independent, cost-effective and time-saving tool for this purpose. Neurofilament heavy chain (NfH(SM135)), astrocytic glial fibrillary acidic protein (GFAP), S100B and ferritin, markers of axonal loss, gliosis, astrocyte activation and microglial activation, respectively, were quantified in the spinal cord homogenates of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE, n=8) and controls (n=7). Levels of GFAP were found to be threefold elevated in CREAE (13 ng/mg protein) when compared to control animals (4.5 ng/mg protein, p<0.001). The inverse was observed for NfH(SM135) (21 ng/mg protein vs. 63 ng/mg protein, p<0.001), ferritin (542 ng/mg protein vs. 858 ng/mg protein, p<0.001) and S100B (786 ng/mg protein vs. 2080 ng/mg protein, N.S.). These findings were confirmed by immunocytochemistry, which demonstrated intense staining for GFAP and decreased staining for NfH(SM135) in CREAE compared to control animals. These findings indicate that axonal loss and gliosis can be estimated biochemically using the newly developed ELISA assays for NfH(SM135) and GFAP. These assays may facilitate the quantification of pathological features involved in neurodegeneration.

Animals↗

PubMed2003

HIV lipodystrophy: prevalence, severity and correlates of risk in Australia.

OBJECTIVE: To establish the prevalence, severity and factors associated with the HIV lipodystrophy syndrome. METHODS: Cross-sectional study of lipodystrophy conducted in high HIV caseload primary care sites and HIV outpatient clinics. A subset of patients was examined using dual energy X-ray absorptiometry (DEXA) and single cut abdominal computerized tomography (CT) at the L4 vertebral level to quantify regional and total body fat. Factors associated with lipodystrophy, lipoatrophy and lipohypertrophy were assessed using multiple logistic regression based on assignment of cases and non-cases. RESULTS: One thousand, three hundred and forty-eight patients (95% male) were surveyed, 20% had AIDS, the mean CD4 lymphocyte count was 486 cells/microL, and 55% had <500 HIV-1 RNA copies/mL. Most participants (87%) had previously received or were currently receiving combination antiretroviral therapy, 73% with at least one protease inhibitor (PI) and 14% a non-PI-containing regimen. Lipodystrophy prevalence was 53% and of these, 55% reported both peripheral lipoatrophy and central lipohypertrophy, 31% experienced peripheral lipoatrophy only and 14% had central lipohypertrophy only. The prevalence of any body habitus change was 62% in PI-experienced patients, 33% in PI-naive patients and 21% in antiretroviral-naive patients. Lipodystrophy severity was less in antiretroviral-naive patients and most severe in PI-experienced patients. Increasing severity of lipodystrophy was both positively and significantly correlated with elevated liver enzymes, decreased testosterone levels, decreased skin-fold thickness, lower levels of total and peripheral fat (DEXA) and higher levels of visceral fat (CT). Lipodystrophy was also significantly associated with increasing age, symptomatic HIV disease, effective viral suppression, and increasing duration of therapy with both nucleoside reverse transcriptase inhibitors and PIs. CONCLUSIONS: The prevalence and severity of lipodystrophy reflects both length and type of treatment with antiretroviral therapy and is associated with decreased testosterone, increases in liver enzymes and greater suppression of HIV RNA. The reports of lipodystrophy in a small percentage of antiretroviral-naive patients suggests that factors other than antiretroviral therapy may be involved in the aetiology of this syndrome or that some conditions, such as wasting or age-associated obesity, may mimic lipoatrophy and lipohypertrophy, respectively.

Absorptiometry, Photon↗

PubMed2003

Cervical screening and health inequality in England in the 1990s.

STUDY OBJECTIVE: s: To examine changing inequality in the coverage of cervical screening and its relation to organisational aspects of primary care and to inequality in cervical cancer incidence and mortality. DESIGN: Retrospective time trends analysis (1991-2001) of screening coverage and cervical cancer incidence and mortality in England. SETTING: The 99 district health authorities in England, as defined by 1999 boundaries were used to create a time series of incidence and mortality rates from cervical cancer per 100 000 population. A subset of 60 district health authorities were used to construct a time series of screening coverage data and GP and practice characteristics. Health authorities were categorised into one of three "deprivation" groups using the Townsend Deprivation Index. PARTICIPANTS: Women aged <35 and 35-64 were selected from health authority populations as the main focus of the study. RESULTS: Cervical cancer screening coverage was consistently higher in affluent areas from 1991-9 but ratio rates of inequality between affluent and deprived health authorities narrowed over time. The increase in coverage in deprived areas was most closely associated with an increase in the number of practice nurses. Cervical cancer incidence and mortality rates were consistently higher in deprived health authorities, but inequality decreased. Screening coverage and cervical cancer rates were highly negatively correlated in deprived health authorities. CONCLUSION: A primary health care intervention such as an organised programme of cervical screening can contribute to reducing inequality in population health.

Adult↗

PubMed2003

Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.

Animals↗