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Biomedical subjects

John M Davis

Publications and source records attributed to John M Davis.

At least 37 records · Page 2Linked to original sources
PubMed2005

Old versus new: weighing the evidence between the first- and second-generation antipsychotics.

In our opinion the best guide to prescribing antipsychotics is the clinician's experience with his patients and in particular the patient being treated. If treatment works, stick with it. We feel it is also important for the clinician to consider the evidence from well-controlled double-blind random-assignment studies because in "evidence-based medicine," biases both known and unknown are controlled by blinding and randomization. The purpose of this paper is to summarize and discuss the evidence on efficacy. Choice of antipsychotic, in our opinion, is probably the most important decision that the clinician makes for the psychotic patient. This involves the choice of drug, its dose, balancing efficacy, side-effects and cost.

Antipsychotic Agents↗
PubMed2005

Imidazenil: an antagonist of the sedative but not the anticonvulsant action of diazepam.

Flumazenil (FLU), a specific benzodiazepine (BZ) receptor antagonist has been used in the treatment of acute BZ intoxication or the alleviation of BZ-induced withdrawal syndrome on the basis of its weak partial agonist action at GABA(A) receptors. However, given to patients, FLU can worsen diazepam-induced withdrawal syndrome by lowering seizure threshold. We therefore investigated whether imidazenil, a selective positive allosteric modulator of GABA action at GABA(A) receptors containing alpha5 subunit, can antagonize diazepam-induced sedative action and suppression of locomotor activity without affecting diazepam anti-bicuculline action. We report here that while FLU (16.5 micromol/kg) showed no effect on locomotor activity and bicuculline-induced convulsion, it completely antagonized diazepam (10.5 micromol/kg) anti-bicuculline action and the suppression of locomotor activity. However, imidazenil (0.76 micromol/kg) elicited anti-bicuculline action and was dose-dependently antagonized by FLU (16.5 and 33 micromol/kg). Furthermore, imidazenil showed no effect on path length traveled but slightly decreased (40%) horizontal activity when compared to diazepam (85%), and maintained the anti-bicuculline action of diazepam to a threshold level similar to that observed with diazepam. Whereas cross-tolerance between BZs has been reported in animals and humans, we previously reported the absence of cross-tolerance between imidazenil and diazepam. Thus, we suggest that imidazenil might be more effective than FLU at alleviating the withdrawal syndrome associated with long-term BZ administration.

Animals↗
PubMed2005

Anticholinesterase (DFP) toxicity antagonism by chronic donepezil: a potential nerve agent treatment.

Animal studies exploring the antagonism of irreversible cholinesterase inhibitors (i.e. nerve agents) such as soman and sarin have shown that pretreatment with the reversible centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic drug, scopolamine, antagonizes the lethality and toxicity of these agents. This study evaluated the effects of pretreatment with the oral cholinesterase inhibitor and anti-Alzheimer's agent, donepezil (Aricept) on the hypokinetic, hypothermic and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor, diisopropylfluorophosphate (DFP) in adult Sprague-Dawley rats. Donepezil (2 mg/kg), given acutely (30 min pretreatment) or chronically (10 daily treatments), significantly antagonized the hypothermia, hypoactivity and diarrhea induced by DFP (1.25 mg/kg) administration. The effects were most prominent 4 and 6 h after the injection of DFP and some protection was observed even when the last treatment of the chronic donepezil protocol was given 24 h before the DFP injection. Although these phenomena are not the same as lethality, they may be parallel phenomena, and our results may have therapeutic implications for the treatment of nerve agent toxicity.

Animals↗
PubMed2005

Minimally effective doses of conventional antipsychotic medications used to treat aggression, self-injurious and destructive behaviors in mentally retarded adults.

Retrospective review of records from 1990 to 1997 revealed unsuccessful attempts to withdraw antipsychotic medications from a total of 34 intellectually disabled individuals. The lowest dose of antipsychotic medication necessary to maintain symptom suppression and the dose at which relapse occurred were noted. Target behaviors observed indicating relapse included increased self-injurious behavior, aggression, and destructive/disruptive behaviors. Nineteen subjects received a low potency antipsychotic agent (ie, thioridazine or chlorpromazine) and 15 received a high potency antipsychotic agent (ie, haloperidol, loxapine, thiothixene). The mean lowest effective dose of chlorpromazine/thioridazine was 149.3 mg/d and relapse occurred at a mean dose of 93.6 mg/d. The mean lowest effective dose of haloperidol or related high potency drugs (expressed as haloperidol equivalents) was 5.9 mg/d, and relapse occurred at a mean dose of 3.8 mg/d.

Adult↗
PubMed2005

Clinical features of 39 patients with antibodies to extractable nuclear antigens despite negative antinuclear antibodies: evidence for autoimmunity including neurologic and connective tissue diseases.

Systemic lupus erythematosus (SLE) rarely presents with a negative antinuclear antibody (ANA). Although antibodies to extractable nuclear antigens (ENA) are sometimes ordered despite a negative ANA, it is unclear if this contributes to the diagnosis of SLE or other forms of connective tissue disease (CTD). We reviewed 39 patients with anti-ENA antibodies despite a negative ANA during a 1-year period to determine the presence of SLE or other CTD. Several patients had clinical features suggestive of CTD, including 1 with possible SLE. A number of patients had neurologic disorders, especially peripheral neuropathy. In this study, the finding of anti-ENA despite negative ANA was associated with neurologic disorders and CTD. This may represent test bias or false-positive anti-ENA assays or false-negative ANA assays, or may imply immune-related mechanisms not previously described.

Adult↗
PubMed2005

Short-term physiological and developmental responses to nitrogen availability in hybrid poplar.

Nitrogen fertilization induces dramatic changes in the growth and development of plants, including forest trees. In this study we examined short-term responses of hybrid poplar, Populus balsamifera ssp. trichocarpa x deltoides, to N fertilization. Glasshouse-grown saplings subjected to limiting, intermediate, and luxuriant levels of ammonium nitrate over a 28 d time course demonstrated rapid changes to whole-plant architecture and biomass accumulation. Nitrogen-associated shifts in allocation occurred in temporally distinct stages. Nitrogen availability modulated parameters that affect carbon gain, including light-saturated net photosynthesis and leaf area. These parameters were affected by N-induced changes to leaf maturation and senescence. Leaf area was also affected by N-induced sylleptic branch development. Genes encoding vegetative storage proteins and starch biosynthetic enzymes exhibited contrasting patterns of expression under differential N availability. A gene encoding a previously uncharacterized putative pectin methylesterase inhibitor displayed expression patterns comparable to the starch biosynthetic genes. The results of this study illustrate the phenotypic plasticity that P. balsamifera ssp. trichocarpa x deltoides exhibits in response to differential N availability.

Carbon↗
PubMed2005

Performance of a self-report measure of the level of response to alcohol in 12- to 13-year-old adolescents.

OBJECTIVE: A low level of response (LR) to alcohol characterizes groups at high risk for alcoholism and predicts future heavier drinking and alcohol-related problems. Because LR might change with increasing age and years of drinking, there is a need to measure this phenotype as early as possible in the drinking career. METHOD: Data were generated from 1,106 12- to 13-year-old subjects in the Avon Longitudinal Study of Parents and Children (ALSPAC). Information about alcohol and other substance use and problems was obtained using a structured interview, and LR from the Self-Rating of the Effects of Alcohol (SRE) questionnaire. RESULTS: Drinking was reported by 80 (7.3% of all subjects) boys and girls. Boys comprised 62.5% of the sample; the mean (SD) age of subjects was 12.9 (0.16) years. Among those 80 drinkers, alcohol had been consumed on an average of 5.4 occasions over the prior 6 months, the average maximum drinks ever imbibed was about 3.3, and 23.8% had any of 26 possible alcohol-related problems. In this group, 36.3% had smoked cigarettes, and 12.5% had used marijuana. The First 5 SRE score among drinkers correlated with the maximum number of drinks consumed at one time at .61 (p < .001), the number of alcohol problems at .25 (p < .01) and the frequency of drinking at .29 (p < .01). When considered along with smoking and marijuana histories, sex and weight, the SRE score contributed significantly to the prediction of maximum drinks per occasion (beta = .60, p < .001) and drinking frequency (beta = .24, p < .05), with a trend (beta = .17, p = .08) for alcohol problems. CONCLUSION: These results support the conclusion that a low LR to alcohol correlates well with the maximum number of drinks consumed even early in the drinking career among individuals for whom acquired tolerance or other factors were unlikely to have explained the relationship.

Adolescent↗
PubMed2004

Serotonergic antidepressant effects on aggressive, self-injurious and destructive/disruptive behaviours in intellectually disabled adults: a retrospective, open-label, naturalistic trial.

There is a growing body of evidence that serotonergic antidepressants are useful in the treatment of maladaptive behaviours in the intellectually disabled. However, not all studies have shown positive results due to lack of efficacy, tolerance development, and troublesome side-effects. The current study consisted of a review of the treatment response to a variety of serotonergic antidepressants, consisting of selective serotonin reuptake inhibitors (SSRIs ) (n = 36) and clomipramine (n = 2) in 38 institutionalized intellectually disabled adults (20 males, 18 females; mean age 45.6 yr, age range 18-74 yr). Those studied were treated for aggression, self-injurious behaviours, destructive/disruptive behaviours, depression/dysphoria, or a combination of these or other challenging behaviours. Most were receiving concurrent psychotropic and/or anticonvulsant medications. Effectiveness was determined by a retrospective review of the summaries of multidisciplinary Neuropsychiatric Behavioural Reviews (NBRs) in which global and specific maladaptive behaviours were rated on a 1- to 7-point scale, and by psychologists' ratings of target behaviours. Overall, statistically significant decreases in the ratings of global maladaptive behaviour and aggression, self-injurious behaviour, destruction/disruption and depression/dysphoria and in psychologists' ratings occurred in the subject group after the initiation of antidepressants. The results suggest that serotonergic antidepressants are useful in the treatment of challenging/maladaptive behaviours in the intellectually disabled.

Adolescent↗
PubMed2004

Pine genes regulated by the necrotrophic pathogen Fusarium circinatum.

A targeted genomics approach was used to construct a cDNA array of potential pathogen-regulated genes for investigating host-pathogen interactions in pine trees (Pinus species). This array, containing a nonredundant set of 311 cDNAs, was assembled by combining smaller sets of cDNAs generated by differential display or suppression subtraction hybridization using a variety of pathogen treatments and elicitors. The array was probed to identify host genes regulated by Fusarium circinatum, a necrotrophic fungus that incited pitch canker disease on pine stems. A set of 29 cDNAs were induced during the disease state. Notably, cDNAs on the array that were derived from experiments with fusiform rust, incited by Cronartium quercuum f. sp. fusiforme (a biotrophic fungus) were unregulated by Fusarium. the results imply distinct genetic responses in pine to diseases incited by necrotrophs and biotrophs. This cDNA collection expands the genomics toolkit for understanding interactions between conifers and their microbial associates in forest ecosystems.

Base Sequence↗
PubMed2004

Antagonism of anticholinesterase (DFP) toxicity by donepezil plus scopolamine: a preliminary study.

Studies in animals exploring the antagonism of the cholinesterase inhibitors soman and sarin have shown that pretreatment with low doses of the centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic agent, scopolamine, is effective against their lethality and toxicity. The current study evaluated the effects of pretreatment with the oral anticholinesterase agent, donepezil (Aricept, 2.0 mg/kg), used to treat Alzheimer's disease, with and without scopolamine in decreasing the hypothermic, hypokinetic, and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor diisopropyl fluorophosphate (DFP, 1.0 mg/kg) in adult Flinders sensitive line (FSL) male rats. Donepezil alone and donepezil plus scopolamine (0.1 mg/kg) to a greater extent antagonized the decrease in temperature, hypoactivity, and induction of diarrhea due to DFP observed at 4 h after its administration. However, donepezil alone induced hypothermia at 1 and 2 h after treatment. Therefore, these preliminary findings are encouraging, but many additional studies are needed to establish the effectiveness of donepezil as a prophylactic agent against irreversible cholinesterase inhibition by DFP.

Animals↗
PubMed2004

Dose response and dose equivalence of antipsychotics.

We review evidence from randomized, placebo-controlled studies of patients with schizophrenia or schizoaffective disorder, which compared 2 or more doses of an antipsychotic to calculate the dose-response curve for each first-generation (typical) antipsychotic (FGA) or second-generation (atypical) antipsychotic (SGA) and as a group (based on dose equivalence). We identified the near-maximal effective dose (ED; ie, the threshold dose necessary to produce all or almost all the clinical responses for each drug). In randomized, fixed-dose studies of SGAs, the near-maximal efficacy dose for olanzapine may be greater than 16 mg; for risperidone, it is 4 mg; and for ziprasidone, it is 120 mg. Risperidone at 2 mg daily is 50% less efficacious than higher doses. Olanzapine at about 6 mg is approximately 33% less effective than higher doses. Aripiprazole at 10 mg daily was fully efficacious. Doses of clozapine well above 400 mg are necessary for optimal treatment of many schizophrenia patients. We found 3.3 to 10 mg haloperidol to be the near-maximal ED range. We find no evidence that doses higher than these are more effective. We failed to find that high doses of haloperidol (or all other first-generation comparison drugs converted to equivalent doses) were less effective than medium doses (3.3 to 10 mg). While high-dose FGAs are not less effective, we feel it is important not to avoid using high dose to avoid excessive toxicity.

Antipsychotic Agents↗
PubMed2004

Physical health monitoring of patients with schizophrenia.

OBJECTIVE: Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings. METHOD: A consensus meeting including psychiatric and other medical experts assembled on October 17-18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis. Experts for each topic area formulated monitoring recommendations that were discussed by all of the participants until a consensus was reached. RESULTS: Consensus recommendations included regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction. Information from monitoring should guide the selection of antipsychotic agents. Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine. Patients who receive both first- and second-generation antipsychotic medications should be examined for extrapyramidal symptoms and tardive dyskinesia. Patients with schizophrenia should receive regular visual examinations. CONCLUSIONS: The conference participants recommended that mental health care providers perform physical health monitoring that typically occurs in primary care settings for their patients who do not receive physical health monitoring in those settings. This change in usual practice is recommended on the basis of the conference participants' belief that this additional monitoring will result in the earlier detection of common, serious risk factors that could, without detection and intervention, contribute to impaired health of patients with schizophrenia.

Adult↗
PubMed2003

Methodological factors influencing measurement and processing of plasma reelin in humans.

BACKGROUND: Reelin, intensively studied as an extracellular protein that regulates brain development, is also expressed in a variety of tissues and a circulating pool of reelin exists in adult mammals. Here we describe the methodological and biological foundation for carrying out and interpreting clinical studies of plasma reelin. RESULTS: Reelin in human plasma was sensitive to proteolysis, freeze-thawing and heating during long-term storage, sample preparation and electrophoresis. Reelin in plasma was a dimer under denaturing conditions. Boiling of samples resulted in laddering, suggesting that each of the 8 repeats expressed in reelin contains a heat-labile covalent bond susceptible to breakage. Urinary-type and tissue-type plasminogen activator converted reelin to a discrete 310 kDa fragment co-migrating with the major immunoreactive reelin fragment seen in plasma and also detected in brain. (In contrast, plasmin produced a spectrum of smaller unstable reelin fragments.) We examined archival plasma of 10 pairs of age-matched male individuals differing in repeat length of a CGG repeat polymorphism of the 5'-untranslated region of the reelin gene (both alleles < 11 repeats vs. one allele having >11 repeats). Reelin 310 kDa band content was lower in subjects having the long repeats in all 10 pairs, by 25% on average (p < 0.001). In contrast, no difference was noted for amyloid precursor protein. CONCLUSIONS: Our studies indicate the need for caution in measuring reelin in archival blood samples, and suggest that assays of plasma reelin should take into account three dimensions that might vary independently: a) the total amount of reelin protein; b) the relative amounts of reelin vs. its proteolytic processing products; and c) the aggregation state of the native protein. Reelin-plasminogen activator interactions may affect their roles in synaptic plasticity. Our results also suggest that the human CGG repeat polymorphism affects reelin gene expression, and may affect susceptibility to human disease.

Blotting, Western↗
PubMed2003

A meta-analysis of the efficacy of second-generation antipsychotics.

BACKGROUND: Consensus panel recommendations regarding choice of an antipsychotic agent for schizophrenia differ markedly, but most consider second-generation antipsychotics (SGAs) as a homogeneous group. It has been suggested that SGAs seem falsely more efficacious than first-generation antipsychotics (FGAs) as a result of reduced efficacy due to use of a high-dose comparator, haloperidol. We performed (1) a meta-analysis of randomized efficacy trials comparing SGAs and FGAs, (2) comparisons between SGAs, (3) a dose-response analysis of FGAs and SGAs, and (4) an analysis of the effect on efficacy of an overly high dose of an FGA comparator. METHODS: Literature search of clinical trials between January 1953 and May 2002 of patients with schizophrenia from electronic databases, reference lists, posters, the Food and Drug Administration, and other unpublished data. We included 124 randomized controlled trials with efficacy data on 10 SGAs vs FGAs and 18 studies of comparisons between SGAs. Two of us independently extracted the sample sizes, means, and standard deviation of the efficacy data. RESULTS: Using the Hedges-Olkin algorithm, the effect sizes of clozapine, amisulpride, risperidone, and olanzapine were 0.49, 0.29, 0.25, and 0.21 greater than those of FGAs, with P values of 2 x 10-8, 3 x 10-7, 2 x 10-12, and 3 x 10-9, respectively. The remaining 6 SGAs were not significantly different from FGAs, although zotepine was marginally different. No efficacy difference was detected among amisulpride, risperidone, and olanzapine. We found no evidence that the haloperidol dose (or all FGA comparators converted to haloperidol-equivalent doses) affected these results when we examined its effect by drug or in a 2-way analysis of variance model in which SGA effectiveness is entered as a second factor. CONCLUSION: Some SGAs are more efficacious than FGAs, and, therefore, SGAs are not a homogeneous group.

Algorithms↗