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Biomedical subjects

P Pratt

Publications and source records attributed to P Pratt.

At least 19 recordsLinked to original sources
PubMed2006

A six-year evaluation of methadone prescribing practices at a substance misuse treatment centre in the UK.

OBJECTIVES: To document changes in prescribing practice at a specialized substance misuse service in the UK occurring since the introduction of the 1999 UK National Guidelines on the management of drug misuse, and to explore a possible link between the length of time spent in methadone maintenance therapy (MMT) and the dosage prescribed. METHODS: A retrospective analysis of a computerized prescription database between 1996 and 2002 obtained from Sheffield Care Trust Substance Misuse Service was performed. The relationship between various measures of dosage and the length of time spent in MMT was investigated. RESULTS: In accordance with the 1999 UK National Guidelines, the proportion of injectable methadone prescribed decreased from 22% to 16%. This was offset by an increase in the prescribing of methadone elixir from 74% to 79%. The 'maximum dose' of methadone prescribed correlated significantly with patient retention, explaining 14% of the variation in time spent in MMT. CONCLUSIONS: Our findings indicate that publication of the UK National Guidelines had a measurable effect on prescribing practice at the Service. We found that a higher methadone dose is associated with increased patient retention in MMT. However, as only a maximum of 14% of the variation in the length of stay is related to methadone dose, the importance of other aspects of treatment such as counselling and rehabilitation programmes, should be considered for the successful treatment of opioid abusers.

Humans↗
PubMed2004

Potential for drug interactions involving cytochromes P450 2D6 and 3A4 on general adult psychiatric and functional elderly psychiatric wards.

AIMS: To assess the potential for interactions involving cytochromes P450 2D6 (CYP2D6) and 3A4 (CYP3A4) between drugs prescribed in a city in-patient psychiatric service. METHODS: Prescription information was obtained from all 236 patients in general adult wards and all 87 patients in functional elderly wards under a city psychiatric service. The frequencies with which combinations of drugs expected to interact via CYP2D6 or CYP3A4 were documented and compared between these two settings. RESULTS: All 2089 drug prescriptions, of which 1237 (59%) were administered, were analyzed. One hundred and seventy-two patients (73%) on adult wards and 59 (68%) on functional elderly wards were prescribed at least one drug metabolized by and/or inhibiting CYP2D6, the difference being nonsignificant (95% confidence interval on the difference -6.3%, 16.4%). Anticipated interactions from 62/82 CYP2D6-related combinations prescribed on adult wards (27/100 patients) and 19/30 prescribed to elderly patients (22/100 patients) were judged to be clinically important or potentially clinically important. The proportion of patients on functional elderly wards prescribed at least one drug interacting with CYP3A4 (87%) was significantly greater than that for patients on adult wards (57%, P < 0.001). The frequency of interactions involving CYP3A4 was significantly greater on functional elderly than adult wards (43/100 vs 22/100 patients, P < 0.025, 95% confidence interval on the difference 4, 38/100). CONCLUSIONS: Our findings confirm extensive polypharmacy on general adult psychiatric and functional elderly psychiatric wards. A substantial proportion of patients were receiving combinations of drugs that interact with CYP2D6 and/or CYP3A4, many of which are known to produce clinically important interactions. Doctors practising in old age psychiatry should be aware that patients on functional elderly wards are at increased risk of clinically important CYP3A4 interactions. Psychiatrists should consider the pharmacokinetic implications of drugs prescribed for use 'as needed', because of the potential for unpredictable interactions.

Adolescent↗
PubMed2000

Regulator of G protein signaling RGS3T is localized to the nucleus and induces apoptosis.

RGS3 belongs to a family of the regulators of G protein signaling (RGS). We previously demonstrated that cytosolic RGS3 translocates to the membrane to inhibit G(q/11) signaling (Dulin, N. O., Sorokin, A., Reed, E., Elliott, S., Kehrl, J., and Dunn, M. J. (1999) Mol. Cell. Biol. 19, 714-723). This study examines the properties of a recently identified truncated variant termed RGS3T. Both RGS3 and RGS3T bound to endogenous Galpha(q/11) and inhibited endothelin-1-stimulated calcium mobilization and mitogen-activated protein kinase activity to a similar extent. However, unlike cytosolically localized RGS3, RGS3T was found predominantly in the nucleus and partially in the plasma membrane. Furthermore, RGS3T, but not RGS3, caused cell rounding and membrane blebbing. Finally, 44% of RGS3T-transfected cells underwent apoptosis after serum withdrawal, which was significantly higher than that of RGS3-transfected cells (7%). Peptide sequence analysis revealed two potential nuclear localization signal (NLS) sequences in RGS3T. Further truncation of the RGS3T N terminus containing putative NLSs resulted in a significant reduction of nuclear versus cytoplasmic staining of the protein. Moreover, this truncated RGS3T no longer induced apoptosis. In summary, RGS3 and its truncated variant RGS3T are similar in their ability to inhibit G(q/11) signaling but are different in their intracellular distribution. These data suggest that, in addition to being a GTPase-activating protein, RGS3T has other distinct functions in the nucleus of the cell.

Animals↗
PubMed1999

Obsessive compulsive disorder, checking, and non-verbal memory: a neuropsychological investigation.

There is considerable evidence in the literature for the presence of non-verbal and praxic memory deficits in OCD. Such deficits may represent the cognitive substrate of doubt-related phenomenon such as checking. Neuropsychological tests of non-verbal memory functioning and memory for actions were administered to patients with OCD (whose predominant symptom was checking) and a group of matched healthy controls. Significant differences were found between the experimental and control groups, suggesting some memory impairment in the OCD group; however, no significant relationship was found linking neuropsychological test indices with checking. Significant relationships were found linking recognition memory problems and immediate memory for actions with general symptom severity.

Adult↗
PubMed1999

The characteristics of asthma education programs within New South Wales.

The aim of the study was to examine the characteristics of asthma education programs within NSW. A cross-sectional questionnaire survey concerning the aims and characteristics of 42 asthma education programs was administered to members of the Asthma Educators Association (AEA) of NSW. While most programs sought to improve asthma knowledge (78%), only a small number sought to improve asthma management skills (38%), asthma control (33%) and attitudes (10%). Most programs performed one-to-one (69%) education. Medical intervention was under-utilized by most programs and only 4% gave feedback to the referring doctor. Program evaluation was incompletely linked to program aims. There was incomplete evaluation of knowledge gain as an outcome. The study reviewed the characteristics of education programs within NSW Existing programs appropriately employ a variety of educational methods and target a broad range of people with asthma. There remains a need to use a combined approach utilizing education and medical management, and to employ methods to evaluate programs.

Adolescent↗
PubMed1999

Get plugged in. East Central Michigan hospitals restore public trust through better communication.

Hoping to regain the confidence of their communities, members of the Hospital Council of East Central Michigan convened a task force of community leaders and hospital representatives, including trustees. One of the task force's first recommendations was to hold focus groups with citizens from around the region. Task force members listened and acted upon their neighbors' concerns.

Community-Institutional Relations↗
PubMed1997

Information-processing, storage characteristics and worry.

Eysenck (1984, Bulletin of the Psychonomic Society, 22, 545-548) suggested that storage characteristics may be an important determinant of worry, and postulated that prolonged worry occurs in individuals who have tightly organised clusters of worry-related information stored in long-term memory. These clusters reflect areas or domains of worry. Because the information is stored in tight clusters, it becomes more accessible, more rapidly activated and therefore retrieved more quickly. The Worry Domains Questionnaire (WDQ) (Tallis, 1991c) is used to determine which domain worried subjects most (Primary) and least (Secondary). Two experiments are reported using a word allocation task, which requires subjects to make categorical decisions, based on these worry domains. It is reported that priming facilitates the emergence of domain effects, thus providing support for a structural hypothesis. High worries take longer to reject negative words if they are from the Primary domain and have difficulty rejecting Primary domain words when they are under a congruent heading. In addition, high worriers are reported to show retarded latencies when attempting to process ambiguous information, consistent with Metzger et al.'s studies (1990, Journal of Clinical Psychology, 48, 76-88). It is suggested that the initiation and maintenance of worry is largely attributable to an elevated evidence requirement and this may link to the personality trait of perfectionism.

Adolescent↗
PubMed1996

Zaprinast, but not dipyridamole, reverses hemodynamic tolerance to nitroglycerin in vivo.

Hemodynamic tolerance to nitroglycerin was developed in spontaneously hypertensive rats following 2-3 days of pretreatment with 100 mg/kg of nitroglycerin administered s.c. 3 times/day. Tolerance was evaluated both in vivo, by administering ascending bolus doses of nitroglycerin of 1-300 micrograms/kg i.v., and ex vivo in isolated, denuded aortic vascular rings by exposure to ascending concentrations of nitroglycerin of 0.0003-100 microM. Tolerance was observed as a significant blunting of the hypotensive and vasorelaxant effect of nitroglycerin. Co-incubation of tolerant aortic rings and pretreatment of tolerant SHR with 10 microM and 0.1-10 mg/kg zaprinast, respectively, resulted in full restoration of the vasorelaxant and hypotensive effect of nitroglycerin. Zaprinast partially reversed hemodynamic tolerance at 0.01 mg/kg. Conversely, dipyridamole (10 microM) reversed tolerance ex vivo, but was ineffective in reversing tolerance in vivo at pretreatment doses of 30 and 60 mg/kg. Following a 100-micrograms/kg i.v. challenge dose of nitroglycerin, aortic cyclic guanosine monophosphate (cGMP) levels were lower in nitroglycerin tolerant SHR when compared to non-tolerant SHR. Pretreatment of tolerant SHR with 10 mg/kg zaprinast restored the increase in cGMP levels to nitroglycerin to that seen in non-tolerant SHR. Conversely, dipyridamole (30 mg/kg) pretreatment was not effective in restoring cGMP levels. These data therefore suggest that reversal of hemodynamic tolerance in vivo is related to restoration of changes in vascular cGMP levels. Zaprinast, a selective cGMP phosphodiesterase inhibitor, effectively reverses tolerance and dipyridamole, a rather non-selective inhibitor, does not.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1991

Following in the right footsteps.

An initiative which targets resources towards chiropody patients with the greatest needs has been taking place in Nottinghamshire during the past three years. Ian Morton and Peter Pratt describe its progress and outline its new goals.

Costs and Cost Analysis↗
PubMed1991

Olfactory acuity in the positive and negative syndromes of schizophrenia.

The olfactory thresholds of 46 schizophrenic subjects were measured. This group yielded 11 patients with a stringently defined positive syndrome and 12 with a negative syndrome when rated with the Positive and Negative Syndrome Scale. The negative group had a significantly (p less than 0.01) higher olfactory threshold than the positive group although neither of the groups differed significantly from a control group. Implications of this finding are discussed.

Adolescent↗
PubMed1990

Characterization of pXV10A, a Copper Resistance Plasmid in Xanthomonas campestris pv. vesicatoria.

The efficacy of copper bactericides for control of Xanthomonas campestris pv. vesicatoria in eastern Oklahoma tomato fields was evaluated. Copper bactericides did not provide adequate control, and copper-resistant (Cu) strains of the pathogen were isolated. The Cu genes in these strains were located on a large indigenous plasmid designated pXV10A. The host range of pXV10A was investigated; this plasmid was efficiently transferred into 8 of 11 X. campestris pathovars. However, the transfer of pXV10A to other phytopathogenic genera was not detected. DNA hybridization experiments were performed to characterize the Cu genes on pXV10A. A probe containing subcloned Cu genes from X. campestris pv. vesicatoria E3C5 hybridized to pXV10A; however, a subclone containing Cu genes from P. syringae pv. tomato PT23 failed to hybridize to pXV10A. Further DNA hybridization experiments were performed to compare pXV10A with pXvCu plasmids, a heterogenous group of Cu plasmids present in strains of X. campestris pv. vesicatoria from Florida. These studies indicated that the Cu genes on pXV10A and pXvCu plasmids share nucleotide sequence homology and may have a common origin. Further experiments showed that these plasmids are distinctly different because pXV10A did not contain sequences homologous to IS476, an insertion sequence present on pXvCu plasmids.

Journal Article↗
PubMed1989

Prevention of detrimental effect of cyclosporin A on vascular ingrowth of transplanted pancreatic islets with verapamil.

The revascularization of pancreatic islet clusters transplanted beneath the renal capsule was studied in a syngeneic mouse model. The degree of vascular ingrowth was visualized by in vivo fluorescence microscopy (fluorescein isothiocyanate-dextran) and judged by a semiquantitative method from coded video recordings. The recipients of isografts were divided into four groups, depending on their daily immunosuppressive treatment: 1) none (controls), 2) 15 mg/kg cyclosporin A (CsA), 3) 0.4 mg/kg verapamil + 15 mg/kg CsA, and 4) 20-30 mg/kg methylprednisolone. In control animals, capillary ingrowth was first demonstrated on day 6, followed by progressive vascularization up to day 34. After 6 mo, the vascular architecture was similar to that seen in normal islets in situ. CsA alone significantly decreased vascular ingrowth on day 14 compared with controls (P less than .02). Verapamil prevented the detrimental effect of CsA (P less than .01), probably by improving renal subcapsular blood flow. Methylprednisolone did not affect revascularization compared with control animals at day 14. We conclude that CsA inhibits vascular ingrowth into transplanted pancreatic islets, which is likely to have clinical implications. The prevention of CsA vascular ingrowth inhibition by a calcium antagonist indicates a possible approach to the correction of this problem, particularly when the renal capsule is used as the recipient's transplant site.

Animals↗
PubMed1982

Selection of the nuclear gene for the mitochondrial adenine nucleotide translocator by genetic complementation of the op1 mutation in yeast.

Oxidative phosphorylation 1 (OP1), a nuclear gene of yeast Saccharomyces cerevisiae which is required for the expression of a functional mitochondria, has been isolated on a recombinant plasmid. The gene was selected from a recombinant plasmid pool which contained wild type yeast genomic DNA by transformation of the yeast nuclear mutant (op1) followed by a two-stage screening procedure. A recombinant plasmid containing a 2.6 kilobase Bam HI fragment of genomic yeast DNA inserted in either orientation into the single Bam HI site of yeast vector YEp 13 could complement the op1 mutation. Analysis of the gene product of this inserted DNA by three independent methods, 1) in vivo expression in Escherichia coli maxicells, 2) cell-free translation of plasmid selected RNA, and 3) expression analysis in yeast, revealed that its gene product is a protein of Mr = 30,000-32,000, which cross-reacts with specific anti-serum to the adenine nucleotide translocator of the mitochondrial inner membrane. The selection procedure is efficient and can be used for the isolation of any defined yeast nuclear gene which participates in mitochondrial development.

Cell Nucleus↗
PubMed1981

Antituberculosis activity of 6 cyclo-octylamino-5,8-quinolinequinone (CQQ).

A new compound, 6 cyclo-octylamino-5,8-quinolinequinone (CQQ), a dual analogue of vitamin K and coenzyme Q, was effective against several drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis. In vitro studies indicated the bactericidal nature of its action at 1 microgram/ml. Pulse exposure studies using M. tuberculosis H37Rv showed that a growth lag period of 96 hours resulted with exposure to 1 microgram/ml for 24 hours or longer.

Mycobacterium tuberculosis↗