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Biomedical subjects

John M Davis

Publications and source records attributed to John M Davis.

49 records · Page 3Linked to original sources
PubMed2003

Laser-light scattering, a new method for continuous monitoring of platelet activation in circulating fluid.

We evaluated a novel technique of laser-light scattering (LLS) to detect platelet-volume changes continuously, reflecting platelet aggregation in circulating fluid. Carotid arteries from 20 dogs were mounted in a dual perfusion chamber. Balloon angioplasty (BA) was performed and arteries perfused with platelet-rich plasma (PRP). A He-Ne laser beam was passed through cuvettes connected to tubing draining the arteries. From the angle of incidence, the average volume of aggregates was measured by the ratio of scattering light at 1 to 5 degrees' spread on the diode array of a multichannel analyzer. Platelet volume varied linearly with the scattered light ratio at 1 to 5 degrees (y = -24.2 + 27.6 x [y = particle size, microm(3); x = scattered light ratio at 1/5 degrees]). For comparison, we used an electronic particle counter (Coulter counter) to measure platelet volume. P-selectin expression was measured to confirm platelet activation. Comparing 10 uninjured and 10 BA-injured arteries, we found that platelet volume as measured with LLS increased from 21.6 +/- 4.1 to 52.1 +/- 12.5 microm(3) (P < .003); as measured with the Coulter counter, it increased from 29.9 +/- 2.4 to 62.3 +/- 7.0 microm(3) (P < .005). Six BA-injured arteries perfused with PRP and aspirin (0.2 mg/mL) were compared with six arteries treated with BA alone. The aspirin decreased platelet volume as measured with LLS from 56.2 +/- 11.8 to 40.2 +/- 12.7 microm(3) (P < .01); the Coulter counter revealed a decrease from 51.9 +/- 18.5 to 38.8 +/- 14.2 microm(3) (P < .001). Coulter counter and LLS results were correlated: r = 0.74, P < .05. The peak of P-selectin expression coincided with peak platelet volume. These data demonstrate that increases in circulating-platelet size stimulated by endovascular injury can be reliably and continuously monitored with the use of LLS.

Angioplasty, Balloon↗
PubMed2003

Effects of topiramate on aggressive, self-injurious, and disruptive/destructive behaviors in the intellectually disabled: an open-label retrospective study.

This study reviews the treatment response to the antiepileptic drug topiramate (Topamax-mean dose 202 mg/d, range 150-350 mg/d) of a group of 22 institutionalized intellectually disabled adults (8 males, 14 females, mean age 46.5 years, age range 25-70 years). These individuals were predominantly classified as having severe or profound intellectual disability and as having a mood disorder. The individuals studied were treated for aggression, self-injurious behaviors, destructive/disruptive behaviors or a combination of these, and/or other challenging and maladaptive behaviors. All subjects were receiving concurrent psychotropic and/or anticonvulsant medications. Effectiveness was determined by retrospective review of summaries of quarterly multidisciplinary Neuropsychiatric Behavioral Reviews. Assignment of global severity scores and evaluation of longitudinal behavioral graphs of target symptoms occurred. Overall, statistically significant decreases in global severity scores and in the cumulative aggression and worst behavior rates occurred in the subjects, especially when the 3 months before and the 3 to 6 months after starting topiramate were compared. The overall subject group showed no significant weight changes. One subject developed delirium, 1 developed hypoglycemia, 1 developed sedation, and 2 developed constipation. The results suggest that topiramate may have a role in the treatment of challenging/maladaptive behaviors in intellectually disabled individuals.

Adult↗
PubMed2003

Olanzapine for self-injurious, aggressive, and disruptive behaviors in intellectually disabled adults: a retrospective, open-label, naturalistic trial.

BACKGROUND: The effectiveness of olanzapine in treating challenging behaviors in the intellectually disabled and its ability to substitute for conventional antipsychotic drugs were evaluated. METHOD: A total of 20 institutionalized adults with a mean age of 42.7 years (range, 18-55 years) with intellectual disability and aggression, self-injurious behavior, destructive/disruptive behavior, or combinations of these behaviors were studied. These individuals were receiving multiple psychotropic medications at baseline and were given additional treatment with the atypical antipsychotic agent olanzapine. The mean dose of olanzapine was 9.1 mg/day (range, 2.5-22.5 mg/day). Effectiveness was determined by retrospective review of the summaries of quarterly neuropsychiatric behavioral reviews and retrospective review of longitudinal behavioral graphs of target symptoms. Data were collected from 1995 to 2000. RESULTS: A significant decrease in global challenging behaviors and specific target behaviors (i.e., aggression, self-injurious behaviors, destructive/disruptive behaviors) occurred (p <.05). A numerical decrease in the dosage of concurrent conventional antipsychotic medications occurred over the course of the first 6 months of olanzapine therapy, and a statistically significant (p <.005) decrease from the start of olanzapine therapy occurred in those subjects who received olanzapine for longer than 6 months (mean = 20.3 months). A significant increase in weight occurred in the subject group during the first 6 months of olanzapine treatment (p <.006), and sedation and constipation were the other common side effects noted. CONCLUSIONS: Olanzapine was found to be effective in the treatment of challenging behaviors in the intellectually disabled and in part could be substituted for administration of conventional antipsychotic drugs.

Adolescent↗
PubMed2003

Choice of maintenance medication for schizophrenia.

Unmedicated schizophrenia patients relapse at a rate of approximately 10% per month. Maintenance treatment with antipsychotic medications can reduce this rate dramatically. Ensuring compliance with medication in the maintenance treatment of schizophrenia encompasses 3 areas of concern: (1) choice of antipsychotic medication, accounting for efficacy and side effects; (2) route of administration of medications, considering the benefits and detriments of long-acting injectable and oral medications; and (3) reducing "doctor noncompliance," the failure of some physicians to perceive the need for long-term treatment for patients with chronic schizophrenia. This article focuses on the selection of the antipsychotic medication that will most likely lead to successful maintenance treatment of schizophrenia. Data from acute trials must be relied upon to evaluate the comparative risks and benefits of these agents as long-term treatments since few double-blind, random-assignment studies have compared the newer-generation antipsychotics for maintenance treatment of schizophrenia. Studies of acute treatment, as well as a small number of studies of maintenance treatment, have shown the newer-generation antipsychotics risperidone and olanzapine to be more efficacious and to have a more favorable side effect profile than conventional-generation antipsychotics. Research on the newer-generation antipsychotics, including ziprasidone, aripiprazole, and quetiapine, shows these agents to be efficacious and safe, although the limited amount of data on these agents precludes a definitive evaluation of their efficacy and safety.

Administration, Oral↗
PubMed2002

Historical studies of premenstrual tension up to 30 years ago: implications for future research.

The biology and treatment of premenstrual tension syndrome has advanced significantly in the past 30 years. Newer research expands on earlier literature that has been accumulated before 1972. This review selectively considers this earlier literature, because it defines the nature and impact of what was then considered to be premenstrual tension syndrome. The authors consider a set of earlier studies that suggest a role for personality, psychodynamics, and cultural variables in the etiology, impact, and treatment of the cyclic disorders. This review also considers studies of the biology of premenstrual tension that suggest a role for sodium and water fluctuations, the renin-angiotensin-aldosterone system, ovarian hormones, monoamines, and acetylcholine. Current applications and potential research directions based on this information are also discussed.

Brain↗
PubMed2002

Thrombostatin, a bradykinin metabolite, reduces platelet activation in a model of arterial wall injury.

OBJECTIVE: Thrombin activates platelets and contributes to the occlusion of arteries following thrombolytic therapy or angioplasty. Thrombostatin (RPPGF), the angiotensin converting enzyme degradation product of bradykinin, inhibits alpha-thrombin induced platelet activation. We hypothesized that thrombostatin prevents platelet aggregation and adhesion after balloon angioplasty (BA). METHODS: Platelet-rich plasma (PRP) was obtained from 22 Beagle dogs before sacrifice and 10% of the PRP was labeled with 111In. Carotid arteries were then removed from each dog and mounted in a dual perfusion chamber and intimal injury was performed with BA. 111In-PRP with or without thrombostatin or aspirin alone was perfused through the arteries for 60 min. During perfusion, platelet volume was measured using a Coulter counter and a laser-light scattering technique. Platelet adhesion to arteries was measured by radioactivity count. RESULTS: Arterial injury alone compared to non-injury increased platelet volume in the circuit by 1.4 times (x) (P<0.05) using a Coulter counter or 1.8x (P<0.05) using laser-light scattering and increased platelet adhesion by 2.3x (P<0.01). When compared to BA injury alone, the addition of thrombostatin reduced platelet volume by 1.8x (P<0.03) as measured by Coulter counter or 1.9x (P<0.01) by laser-light scattering and platelet adhesion by 4.2x (P<0.05). Compared to BA injury alone, aspirin reduced platelet volume by 1.2x (P<0.01) as assessed by Coulter counter or 1.5x (P<0.03) using laser-light scattering and platelet adhesion by 1.8x (P<0.02). CONCLUSION: Thrombostatin or aspirin independently decreases evidence of platelet activation in the canine carotid artery model of BA injury.

Animals↗
PubMed2002

A new method for measuring inhibition of platelet function by nonsteroidal antiinflammatory drugs.

Aspirin is widely used to help prevent vascular occlusion caused by atherosclerotic vascular disease. We used a platelet-aggregation assay (PAA) to evaluate the reliability of a proprietary platelet agonist, platelet prostaglandin agonist (PPA), to detect the amount of platelet inhibition induced by four different classes of nonsteroidal antiinflammatory drugs (NSAIDs) with antiplatelet effects. Twenty normal donors were evaluated before and 24 hours after ingestion of 325 mg of aspirin. With 125 micromol/L PPA, the slope of the PPA-PAA curve completely differentiated aspirin-treated from normal platelets. The aspirin platelet slope, 27.9 +/- 2.0 (range 5.5-47), was significantly decreased (P <.001) compared with the findings before administration of aspirin, 75 +/- 3.1 (range 50-125). Additionally, the time elapsed before 50% platelet aggregation (T(50)) with aspirin, 10.1 +/- 0.7 minutes (range 4.7-17), was significantly prolonged (P <.05) compared with the mean time before administration of aspirin (4.2 +/- 0.2 minutes, range 1.7-6.4). Aspirin in a daily dosage of 325 mg for 14 days produced significantly greater inhibition of PPA-PAA than that induced by a single 325-mg dose (P <.001). The long-term platelet-inhibitory effects of aspirin in 9 normal volunteers were evaluated with PPA-PAA 2, 8, 24, 48, 72, and 96 hours after a single dose of aspirin, 81 or 325 mg. Compared with the preaspirin slope, 79.6 +/- 1.9, the maximal decrease in slope occurred after 2 hours for both 81 mg (61.3 +/- 6.7) and 325 mg (12.1 +/- 1.8). The decreased slopes and increased T(50) observed at 2, 8, and 24 hours (P <.001) reflected the greater degree of platelet inhibition with 325 mg than with 81 mg aspirin. Inhibition of PPA-PAA was observed with nonaspirin nonsteroidal antiinflammatory drugs (NNSAIDs), but, compared with aspirin, the inhibition was minimal. PPA-PAA may be used to help measure the magnitude of NSAID-induced inhibition of platelets.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Clinical profile of an atypical antipsychotic: risperidone.

Stimulated by Dawkins and colleagues' (1999) and Remington and Kapur's (2000) calls to develop clinical profiles of the new atypical antipsychotic drugs and by Mattes's critiques (1997, 1998), we performed two sets of analyses for risperidone. First, we reanalyzed data from the North American risperidone trial: risperidone was superior to haloperidol to an equal degree in patients with and without the deficit syndrome, in patients with paranoid and nonparanoid schizophrenia, in treatment-resistant and treatment-responsive patients (patients hospitalized for longer and shorter periods), and in patients with or without weight gain. Moreover, risperidone was more effective than haloperidol on symptoms nonresponsive and responsive to haloperidol; its effects on negative symptoms were independent of its effects on extrapyramidal symptoms; and it was effective in treating depression in schizophrenia. Second, we performed a meta-analysis of 18 controlled risperidone trials: risperidone was consistently more effective than conventional antipsychotics in treating positive and negative symptoms.

Antipsychotic Agents↗
PubMed2002

The Mount Sinai conference on the pharmacotherapy of schizophrenia.

This report summarizes the recommendations from a consensus meeting that focused on specific questions regarding the pharmacotherapy of schizophrenia. The issues were selected because there was evidence that experts had recently disagreed about the evidence supporting a particular practice or when there were substantial variations in a clinical practice indicating that there was disagreement among clinicians. The group of experts was able to reach a consensus regarding the evidence base pertaining to the following issues: First generation (FGAs) and second generation (SGAs) antipsychotics as first line agents; the duration of antipsychotic trials; the effectiveness of clozapine and other agents for treatment refractory schizophrenia; risk of tardive dyskinesia on FGAs and SGAs; differences among antipsychotics for different dimensions of psychopathology; and side effect monitoring for various antipsychotics.

Antipsychotic Agents↗
PubMed2002

Pathogen challenge, salicylic acid, and jasmonic acid regulate expression of chitinase gene homologs in pine.

To better understand the molecular regulation of defense responses in members of the genus Pinus, we tested the expression of various chitinase homologs in response to pathogen-associated signals. PSCHI4, a putative extracellular class II chitinase, was secreted into liquid medium by pine cells and was also secreted by transgenic tobacco cells that ectopically expressed pschi4. Extracellular proteins of pine were separated by isoelectric focusing; PSCHI4 was not associated with fractions containing detectable beta-N-acetylglucosaminidase or lysozyme activities. However, other fractions contained enzyme activities that increased markedly after elicitor treatment. The pschi4 transcript and protein accumulated in pine seedlings challenged with the necrotrophic pathogen Fusarium subglutinans f. sp. pini, with the protein reaching detectable levels in susceptible seedlings concomitant with the onset of visible disease symptoms. Additional chitinase transcripts, assigned to classes I and IV based on primary sequence analysis, were also induced by pathogen challenge. Jasmonic acid induced class I and class IV but not class II chitinase, whereas salicylic acid induced all three classes of chitinase. These results show that multiple chitinase homologs are induced after challenge by a necrotrophic pathogen and by potential signaling molecules identified in angiosperms. This suggests the potential importance of de novo pathogenesis-related (PR) gene expression in pathogen defense responses of pine trees.

Amino Acid Sequence↗
PubMed2002

A multidose study of haloperidol decanoate in the maintenance treatment of schizophrenia.

OBJECTIVE: Maintenance medication is critical in the prevention of psychotic relapse and rehospitalization among patients with schizophrenia. Given potential adverse effects, identification of the minimum effective dose is clinically important. METHOD: A multicenter, double-blind study was conducted to determine rates of symptomatic exacerbation and adverse effects in 105 outpatients with schizophrenia randomly assigned to four different fixed doses of haloperidol decanoate and treated for 1 year or until relapse. The doses used were 25, 50, 100, and 200 mg given intramuscularly once per month. RESULTS: Rates of symptomatic exacerbation were 15% in the 200-mg group, 23% with 100 mg, 25% with 50 mg, and 60% with 25 mg. No significant differences in outcome were found between the groups treated with 200, 100, and 50 mg. Among the patients who completed the trial with no symptomatic exacerbation, there were no differences between dose groups on measures of psychopathology at the final rating point. CONCLUSIONS: The results of this study suggest that the 200-mg/month dose of haloperidol decanoate is associated with the lowest rate of symptomatic exacerbation (15%) with minimal increased risk of adverse effects or subjective discomfort in comparison to 100 or 50 mg. At the same time, the rates of worsening with 100 mg (23%) and 50 mg (25%) were not significantly greater than that seen with 200 mg. These results provide some guidance as to effective dose ranges of haloperidol decanoate.

Adult↗
PubMed2002

Development of a sensitive immunoradiometric assay for detection of platelet surface-associated immunoglobulins in thrombocytopenic dogs.

OBJECTIVE: To develop a direct assay to measure platelet surface-associated immunoglobulins (PSAIg) in dogs and to determine whether the assay is useful in the diagnosis of immune-mediated thrombocytopenia (IMT). ANIMALS: 20 healthy dogs were used to develop reference intervals, and 23 dogs with IMT and 17 with non-IMT were used to evaluate the clinical use of this assay. PROCEDURE: After optimization of platelet collection and assay conditions, concentrations of PSAIg were measured, using radiolabeled staphylococcal protein A (SpA) and polyclonal antibodies against canine IgG (anti-gamma) and IgM (anti-micro). Concentrations of PSAIg were expressed as the percentage of radiolabeled immunoglobulin detector bound. RESULTS: Cut-off values (mean + 3 SD) were as follows: SpA, 1.1%; anti-gamma, 1.3%; and anti-micro, 3.5%. Values greater than these cut-off values were considered positive. Values determined by use of radiolabeled SpA for all dogs with IMT were greater than the cut-off value; values were considered high positives (> 5 times cut-off value) for 22 of these 23 dogs. Although 9 of 17 dogs with non-IMT also had PSAIg concentrations greater than the cut-off value, values were considered high positives for only 3 of these 9 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The immunoradiometric assay developed is a reliable and sensitive method to detect PSAIg in dogs. However, to obtain accurate results, optimum temperature, time, and storage conditions must be used. Detection of increased concentrations of PSAIg in dogs presumed to have non-IMT should alert clinicians to reconsider an immune-mediated basis for the thrombocytopenia.

Animals↗