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Biomedical subjects

C M Davis

Publications and source records attributed to C M Davis.

At least 19 recordsLinked to original sources

Comparison of haloperidol and reduced haloperidol plasma levels in four different ethnic populations.

1. Plasma haloperidol and reduced haloperidol concentration were measured in four ethnic populations. 2. Plasma samples were obtained under steady-state conditions and obtained 10-12 hours post bedtime dose and prior to the morning dose. 3. Haloperidol and reduced haloperidol plasma levels were assayed by radioimmunoassay and liquid chromatography. 4. A wide interpatient variability between haloperidol dose and plasma concentration was observed for each ethnic group. 5. The Chinese group differed from the other ethnic populations. 6. A nonlinear relationship was observed between haloperidol and reduced haloperidol plasma levels in each ethnic group. Further, the relationship of haloperidol to reduced haloperidol plasma levels differed for each ethnic group. These results suggest that various ethnic groups could metabolize haloperidol and reduced haloperidol differently.

Black or African American

Microbial etiology of acute pneumonia in hospitalized patients.

The purpose of this study was to determine the microbial etiology of pneumonia by using strict criteria among a group of hospitalized patients. Patients with acute community-acquired or hospital-acquired pneumonia were studied in a systematic and comprehensive manner for bacterial, viral, chlamydial, mycobacterial, and fungal pathogens. A total of 198 patients with 204 episodes of pneumonia were evaluated. Despite 100 percent follow-up of all surviving patients, a specific etiologic agent could be found in only 103 episodes. Among 154 episodes of community-acquired pneumonia, a diagnosis was made in 79; the most common pathogen was from the genus Legionella, followed by various Gram-negative enteric bacteria, Gram-positive cocci, influenza A virus, and Mycoplasma pneumoniae. The etiologic agent was found in 24 of the 50 patients with hospital-acquired pneumonia; no pathogen predominated. We conclude that even when elaborate diagnostic studies are done, including many invasive procedures, the etiology can be determined in only about half of the patients with acute pneumonia. The pathogens of pneumonia in this study are not markedly different between community-acquired and hospital-acquired infection.

Acute Disease

"America responds to AIDS," but did college students? Differences between March, 1987, and September, 1988.

To assess thoughts, perceptions, attitudes, and behavior related to AIDS, data were collected from 2 similar samples of college students. The sets of data were collected 18 months apart. Results indicate increased awareness and knowledge and changed attitudes and behaviors in some cases, but the absolute magnitudes of the differences are small for most between-group comparisons. Also, the evidence suggests that many students lack detailed knowledge and fail to see the implications of their knowledge for change in their own behavior. These findings imply educational efforts must go beyond merely providing knowledge and explicitly link facts to personal belief systems and decision making.

Acquired Immunodeficiency Syndrome

Improving smoking cessation counseling by family practice residents.

BACKGROUND: While programs to train residents in smoking cessation counseling skills have been devised, few have assessed trainee behavioral changes in practice settings where residents were blind to the evaluation of their behavior. This study assessed the effectiveness of a training program in smoking cessation counseling and chart-prompting system in increasing the frequency and quality of counseling by residents at three clinic sites. METHODS: Twenty-eight residents participated in a training program that included epidemiology, discussion of attitudes, counseling techniques, videotaped examples, and small group role play. The chart-prompting system was implemented at two clinics 1 month after training. Patient exit interviews, during which information on resident counseling on smoking cessation was obtained, were conducted before training, after training, at 3-month follow-up, and at 6-month follow-up. Questionnaires assessing knowledge, attitudes, and self-perceived counseling behaviors were completed by residents at pretraining, posttraining, and 6-month follow-up periods. RESULTS: Interviews with 517 smokers were analyzed. Results showed an increase in counseling at 3-month follow-up but a regression toward baseline at 6 months. Counseling improved at clinics where chart prompting was initiated. The number of counseling behaviors decreased when the number of patients seen increased. Whether a patient received counseling was positively associated with prior contact with the physician. There was no correlation between resident self-perception and patient report. CONCLUSIONS: A training program in smoking cessation counseling and a chart-prompting system did not result in a lasting change in resident behavior. System factors may play an important role in long-term behavior change.

Clinical Competence

A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene.

Several hormones, including insulin, glucagon, and glucocorticoids, regulate the expression of the rate-limiting gluconeogenic enzyme, phosphoenolpyruvate carboxykinase [GTP: oxaloacetate carboxy-lyase (transphosphorylating); EC 4.1.1.32; PEPCK] in liver. In this report we demonstrate that retinoic acid (RA) also regulates PEPCK expression by inducing a 3-fold increase in the rate of transcription of the PEPCK gene. A RA response element located between -468 and -431 in the PEPCK promoter mediates a 7-fold increase in expression of a chimeric construct containing the basal PEPCK promoter ligated to the chloramphenicol acetyltransferase reporter gene. This element confers RA responsiveness through the heterologous thymidine kinase promoter and functions relatively independent of position and orientation. An 18-base-pair core sequence (-451 to -434) (i) mediates an effect of RA on PEPCK gene expression and contains motifs found in two other RA response elements; (ii) corresponds to AF1, an accessory factor element that is an integral component of the complex glucocorticoid response unit in the PEPCK gene promoter; (iii) is in a region involved in the developmental expression of the PEPCK gene; and (iv) shows homology to elements involved in the tissue-specific regulation of genes, including the hepatic apolipoprotein genes and the alpha 1-antitrypsin gene.

Animals

Identification and partial characterization of laminin binding proteins in immature rat Sertoli cells.

Laminin, a major component of basement membrane extracellular matrices, promotes differentiation in a number of cell types, including Sertoli cells. We have identified and characterized Sertoli cells. We have identified and characterized Sertoli cell surface molecules which interact with laminin. Using laminin-Sepharose affinity chromatography and [125I]laminin binding to Sertoli cell plasma membranes, binding proteins have been identified with the Mr 110,000, 67,000, 55,000, 45,000, 36,000, and 25,000. In addition, the Mr 110,000 and 67,000 laminin binding proteins were phosphorylated. The 67,000, 45,000, and 36,000 react with antibodies to the previously characterized laminin receptor and these antibodies stain the basolateral surface of Sertoli cells in vivo. Cultured Sertoli cells stain for laminin receptor both on the cell surface and within the cells. Antiserum to the 32,000 and 67,000 laminin binding proteins partially inhibited spreading of Sertoli cells on a laminin-coated culture dish, suggesting a functional importance of those proteins in Sertoli cell differentiation. The 25,000 and 45,000 laminin binding proteins reacted with integrin antibodies, but no high-molecular-weight forms could be detected. Integrin was localized to the cell surface and intracellularly but antibodies did not block Sertoli cell spreading on laminin. This work represents the first identification and characterization of extracellular matrix binding proteins in an endocrine organ and suggests an important role for the nonintegrin 32/67 laminin binding proteins.

Amino Acid Sequence

Thiothixene pharmacokinetic interactions: a study of hepatic enzyme inducers, clearance inhibitors, and demographic variables.

Fifty-nine plasma thiothixene concentrations were measured in 42 patients as part of routine therapeutic drug monitoring. Data collection included concomitant medications, smoking history, and demographic variables. A retrospective analysis was performed to assess the effect of these parameters on oral thiothixene clearance. When groups of patients were categorized by concomitant medications (i.e., no interacting drugs, enzyme/clearance inducers, and enzyme/clearance inhibitors), thiothixene clearance was found to be significantly increased by enzyme inducing drugs (e.g., anticonvulsants) and decreased by clearance inhibiting agents (e.g., cimetidine). Tobacco smoking significantly increased the hepatic clearance of thiothixene within the no interactions and inhibitor groups, but not in the inducer group. Significantly more patients in the inducer group had nondetectable plasma concentrations of thiothixene than the other groups. When the entire patient population was dichotomized by age, patients less than 50 years old had a significantly greater mean clearance (48.2 +/- 37.8 liters/min) versus those greater than or equal to 50 (20.0 +/- 12.6 liters/min). Men in this cohort exhibited a significantly higher clearance (49.2 +/- 38.7 liters/min) than did the women (22.0 +/- 13.5 liters/min). By taking into account these potential sources of pharmacokinetic variability when monitoring plasma thiothixene concentrations, more appropriate dosing of thiothixene may be achieved. Controlled, prospective studies are needed to validate these findings.

Administration, Oral

The use of selegiline in Alzheimer's patients with behavior problems.

BACKGROUND: Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer's disease that does not cause significant patient sedation. Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens. The purpose of this study was to document the efficacy of selegiline in Alzheimer's patients with behavior problems. METHOD: Eight Alzheimer's patients (6 women and 2 men) ranging in age from 50 to 82 years (mean +/- SD = 74.0 +/- 10.5) were enrolled in this single-blind study. Patients received selegiline 10 mg each day for 8 weeks. Prior to drug administration and at the end of Weeks 1, 2, 4, 6, and 8, patients were evaluated for behavior (BEHAVEAD), cognitive function (Mini-Mental State Examination), and caregiver stress (Caregiver Burden Scale). RESULTS: Of eight enrolled patients, five were available for analysis. No statistically significant differences were found between mean baseline and mean 8-week scores for any of the three tests. However, clinical significance was noted by improvement in cognition (orientation and recall), caregiver stress, and behavior. Behavior was noted to improve in the areas of paranoid and delusional ideation, hallucinations, activity disturbances, anxiety, and phobias. CONCLUSION: These data suggest that some Alzheimer's patients with behavior problems may benefit from selegiline therapy.

Aged

Granuloma faciale. Comparison of different treatment modalities.

Granuloma faciale is an uncommon cutaneous condition characterized by brownish-red macules, papules, nodules, and plaques. Separate areas of granuloma faciale involving the nasal skin of a 32-year-old man were treated using electrosurgery, carbon dioxide laser, and dermabrasion. All modalities provided good cosmetic and functional outcomes. The relative advantages and disadvantages of each technique are presented.

Adult

What is empathy, and can empathy be taught?

Empathy is a commonly used, but poorly understood, concept. It is often confused with related concepts such as sympathy, pity, identification, and self-transposal. The purposes of this article are to clearly distinguish empathy from related terms and to suggest that the act of empathizing cannot be taught. According to Edith Stein, a German phenomenologist, empathy can be facilitated. It also can be interrupted and blocked, but it cannot be forced to occur. What makes empathy unique, according to Stein, is that it happens to us; it is indirectly given to us, "nonprimordially." When empathy occurs, we find ourselves experiencing it, rather than directly causing it to happen. This is the characteristic that makes the act of empathy unteachable. Instead, promoting attitudes and behaviors such as self-awareness, nonjudgmental positive regard for others, good listening skills, and self-confidence are suggested as important in the development of clinicians who will demonstrate an empathic willingness.

Attitude of Health Personnel

Differential expression of extracellular matrix components in rat Sertoli cells.

We studied expression of laminin, fibronectin, and Type IV collagen in the testis by means of immunofluorescence and immunoblot analysis and also examined gene expression of fibronectin using the ribonuclease protection assay. By immunofluorescence on sections from 20-day-old rats, laminin, fibronectin, and Type IV collagen were found in the basement membrane of the seminiferous tubules and in the interstitial regions of the testis. No localization of any extracellular matrix components was found inside the sectioned cells. However, when Sertoli cells were cultured on glass coverslips, laminin and Type IV collagen were both found inside the cells, suggesting new synthesis. In cultured peritubular cells, Type IV collagen, laminin, and fibronectin were found within the cells. When examined by immunoblot analysis, freshly isolated Sertoli and peritubular cells from 20-day-old rats did not demonstrate production of laminin or fibronectin. After 5 days in culture, peritubular cells produced both laminin and fibronectin, whereas cultured Sertoli cells produced only laminin. In contrast, freshly isolated and cultured Sertoli and peritubular cells all produced Type IV collagen. Moreover, the ribonuclease protection assay indicated that the bulk of fibronectin gene expression occurs within the first 10 days of postnatal development, with lower maintenance levels occurring thereafter. These results indicate that in the testis the highest levels of expression of laminin and fibronectin occur during development and in primary cell culture, whereas expression of Type IV collagen is higher at later stages.

Animals

Kinetics and clinical evaluation of haloperidol decanoate loading dose regimen.

We have evaluated the efficacy and safety of different dosing regimens of haloperidol decanoate (HLD). Eighteen patients were evaluated as part of our ongoing Therapeutic Drug Monitoring Program. Diagnoses were chronic schizophrenia (n = 12), bipolar with psychosis (n = 3), and others (n = 3). Patients were assessed prior to each HLD dose using the Clinical Global Impressions (CGI) rating scale. The total monthly HLD dose for our population was calculated based on a target conversion ratio of 20 times the previously administered oral haloperidol dose given in divided doses of 100 mg to 150 mg every 3 to 7 days until the full amount was administered. This HLD dosing pattern was repeated during the second month, but at a lower dose to compensate for drug accumulation. Despite this loading dose paradigm, significantly greater haloperidol plasma concentrations were present during oral haloperidol than during the first month of HLD therapy. This regimen achieves therapeutically equivalent plasma concentrations (Cps) more rapidly following conversion from oral haloperidol than standard dosing procedures. A series of cases and pharmacokinetic simulations are used to illustrate the therapeutic relationship of dosing to plasma concentrations.

Adult

Rat gene 33: analysis of its structure, messenger RNA and basal promoter activity.

Several overlapping cDNA and genomic DNA clones corresponding to mRNA g33 and gene 33, respectively, were isolated and characterized. The mRNA g33 molecule is 2971 nt in length, exclusive of a poly(A+) tail, and encodes a putative 459 amino acid protein (49,946 daltons). The 13.2 kbp gene consists of four exons, three introns, and has two initiation sites located 27 and 30 bp downstream from a TATA box. Transfection of H4IIE cells with a fusion gene 33 (-1900 to +32)/luciferase construct (pSL330A) gave rise to readily detectable luciferase activity. In addition, primer extension analysis of the gene 33/luciferase mRNA transcribed in these experiments showed that transcription initiates in the gene 33 DNA at two sites consistent with those found in vivo. Analysis of the effect of 5' deletions on basal promoter activity showed that, in relation to the promoter activity of pSL330A, approximately 40% of the activity is lost between -1643 and -1050, another approximately 40% between -550 and -475, and deletion to -55 causes a total loss of detectable luciferase activity.

Amino Acid Sequence

Eye movements in cocaine abusers.

Using electro-oculography, we quantitatively investigated eye movements in nine heavy cocaine abusers and three groups of controls. Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of brain norepinephrine, in cocaine abusers were reduced to an average of 53% of normal. Cocaine abusers had normal smooth pursuit, optokinetic nystagmus, vestibulo-ocular reflex, visual suppression of the vestibulo-ocular reflex, and caloric nystagmus. Data were suggestive of a significant reduction in the degree of immediate enhancement of visual-vestibulo-ocular reflex gain by magnified vision in the cocaine abusers. However, adaptive plasticity of the vestibulo-ocular reflex was normal in the cocaine abusers. These results suggest that, despite animal data linking vestibulo-ocular reflex plasticity to central norepinephrine, this neurotransmitter may not be important to plasticity in human beings.

Adult

Clinical implications of increased antipsychotic plasma concentrations upon anticonvulsant cessation.

Plasma antipsychotic concentrations were measured in five patients when their anticonvulsant medications were discontinued. Plasma antipsychotic concentrations increased by two- to five-fold at 4 weeks after cessation. All patients demonstrated either moderate or marked improvement as antipsychotic plasma concentrations increased. Four patients experienced extrapyramidal side effects within 30 days of anticonvulsant discontinuation. Careful monitoring of clinical symptoms, adverse effects, and plasma antipsychotic concentrations is recommended.

Adult

Haloperidol and reduced haloperidol plasma levels in Chinese vs. non-Chinese psychiatric patients.

Haloperidol and reduced haloperidol plasma concentrations were measured in age-matched Chinese and non-Chinese patients (n = 32). Steady-state plasma concentrations were obtained 10-12 hours after the bedtime dose. Haloperidol and reduced haloperidol concentrations were measured by liquid chromatography and radioimmunoassay. Haloperidol plasma concentrations did not significantly differ between the populations, but reduced haloperidol levels were 3 times greater in non-Chinese patients than in Chinese patients. The incidence of extrapyramidal side effects was higher in Chinese patients (18 vs. 10), while non-Chinese patients with extrapyramidal symptoms had higher reduced haloperidol plasma levels. Logistic regression analysis revealed that ethnicity and reduced haloperidol/haloperidol ratios were important variables in predicting extrapyramidal symptoms. These results suggest that the metabolism and disposition of haloperidol and reduced haloperidol could differ among ethnic populations.

Adult

Activation and demethylation of the intracisternal A particle genes by 5-azacytidine.

Treatment of C3H 10T1/2 mouse embryo fibroblasts with the cytidine analogues 5-azacytidine and 5-aza-2-deoxycytidine causes altered gene expression and results in the manifestation of phenotypic changes and altered cell morphology. This includes the conversion of these cells to adipocytes, chondrocytes and myotubes. The effects of these analogues on intracisternal A particle (IAP) gene expression in mouse C3H 10T1/2 cells have been examined. Treatment with either 3 microM 5-azacytidine or 0.3 microM 5-aza-2-deoxycytidine for 24 h was associated with an immediate increase in IAP gene transcription, and with the subsequent appearance of IAPs in the cisternae of the cells 24 h after removal of the drug. Control cells contained no, or very few, IAPs and IAP mRNA. Analysis of the methylation status of the IAP genes, using the restriction endonucleases HpaII, MspI and HhaI, showed that these genes were already demethylated at the end of the 24-h treatment period. IAP gene transcripts were detectable even after a 16-h drug treatment period, at which stage the genes were not yet fully demethylated. After further growth in fresh medium for 90 h, the levels of IAP RNA started to decline, but the demethylated CpG sites were not yet remethylated. These results suggest the involvement of other factors, in addition to methylation, in the regulation of IAP gene expression. These drugs were found to have no stimulatory effect on several oncogenes examined in this study.

Animals