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Biomedical subjects

Francisco J Diaz

Publications and source records attributed to Francisco J Diaz.

At least 19 recordsLinked to original sources
PubMed2007

Individualizing drug dosage by using a random intercept linear model.

An algorithm for drug dosage individualization is proposed. The algorithm assumes a random intercept linear model for the log of trough-plasma-concentration-to-dosage ratio of the drug at steady-state, and aims at determining an optimum dosage for producing a trough steady-state plasma concentration within a target concentration range. The minimum number of algorithm steps necessary to find the optimum dosage is computed. Computations are illustrated for clozapine, an antipsychotic drug used to treat patients with severe schizophrenia.

Algorithms↗
PubMed2007

Weight gain during a double-blind multidosage clozapine study.

Possible variables associated with weight gain during clozapine treatment include dosing, treatment duration, baseline body mass index (BMI), sex, and plasma norclozapine concentrations. Weight gains during a double-blind, randomized clozapine study using 100-, 300-, and 600-mg/d doses were analyzed. It was hypothesized that weight gain was associated with baseline BMI, clozapine dosing, and demographic factors. The possible contribution of plasma clozapine and norclozapine concentrations was explored. Fifty treatment-refractory schizophrenia patients were randomized to 100-, 300-, or 600-mg/d doses of clozapine for a 16-week, double-blind treatment in a research ward. Nonresponsive patients went onto a second and/or a third 16-week, double-blind treatment at the other doses. Weights of patients were measured every week. During the first clozapine treatment, weight gain varied across 3 baseline BMI categories (normal-weight patients [4.1 kg, P < 0.001], overweight patients [2.6 kg, P = 0.05], and obese patients [0.36 kg, not significant]) and according to dosing (600 mg/d [4.4 kg], 300 mg/d [2.6 kg], and 100 mg/d [1.3 kg]). Sex had no effect after controlling for baseline BMI and dose, but the African-American race had a strong significant effect despite the small number of African Americans (n = 6). At the end of the first clozapine treatment, plasma norclozapine concentration was not significantly correlated with weight gain in the total sample (r = 0.16, P = 0.32, n = 43), but seems to be strongly correlated in nonsmokers. Despite its limitations, this study indicates that baseline BMI, dosing, and, possibly, the African-American race may be major determinants of clozapine-induced weight gain.

Antipsychotic Agents↗
PubMed2006

Does smoking reduce akathisia? Testing a narrow version of the self-medication hypothesis.

BACKGROUND: The self-medication hypothesis proposes that schizophrenia patients smoke to decrease their schizophrenia symptoms or antipsychotic side effects, but they usually start smoking before their illness and heavy smoking is not consistently associated with fewer symptoms or side effects. A narrow version of the self-medication hypothesis, heavy smoking reduces akathisia, is explored. METHOD: The sample included 250 outpatients with DSM-IV schizophrenia assessed with the Positive and Negative Syndrome Scale (PANSS) and the Barnes Akathisia Scale. Prevalences were 69% (173/250) for smoking, 39% (98/250) for heavy smoking (> or =30 cigarettes/day), 7% (17/250) for akathisia (Barnes Global score>1), 14% (35/250) for a broader akathisia definition (Barnes Global score>0) and 20% for excited symptoms (>1 on the PANSS factor score). RESULTS: Heavy smoking was not associated with akathisia (41% of patients with akathisia were heavy smokers versus 39% of patients without akathisia; chi2=0.3, df=1, p=0.86), even after correcting for confounding factors and/or using a broader akathisia definition. Heavy smoking was associated with excited schizophrenia symptoms (possibly reflecting agitation). Particularly in patients taking lower doses of typical antipsychotics, excited symptoms, with or without akathisia, were strongly associated with heavy smoking and appear to interact with patients' reports of smoking's calming effect as the main reason for smoking. CONCLUSION: The self-medication hypothesis does not explain increased smoking and heavy smoking in schizophrenia. Moreover, heavy smoking may be associated with more disturbed brain homeostatic mechanisms. Prospective studies need to explore whether temporary increases in cigarette smoking may be associated with periods of higher agitation, with or without akathisia.

Adult↗
PubMed2006

Fewer but heavier caffeine consumers in schizophrenia: a case-control study.

According to the literature, there is an association between schizophrenia and caffeine consumption, but it is not clear whether schizophrenia is associated with either higher prevalence of daily caffeine intake or the amount consumed. In this study we compared our previously published schizophrenia patients (n=250) with a control sample (n=290) after controlling for demographic variables and tobacco and alcohol consumption. Current caffeine intake was less frequent in schizophrenia patients (59%, 147/250) than in controls (70%, 204/290). In the multivariate analyses, caffeine intake was less frequent at an older age and in schizophrenia patients, and more frequent in smokers and alcohol users. Among caffeine consumers, heavy caffeine intake (> or =200 mg/day) was significantly associated with schizophrenia (64%, 94/147 in schizophrenia versus 36%, 73/204 in controls), as well as older age and smoking. Daily amount of caffeine intake and smoked cigarettes correlated significantly in the schizophrenia group but not in the control group; the correlation of caffeine intake with nicotine dependence was low and non-significant in both groups. The association between current smoking and heavy caffeine intake may be partly explained by a pharmacokinetic effect: tobacco smoke compounds induce caffeine metabolism by the cytochrome P450 1A2. Although schizophrenia by itself may be associated with heavy caffeine intake in caffeine users, part of this association was explained by the association between schizophrenia and smoking. The relationship between caffeine and alcohol intake appeared to be more complex; alcohol and caffeine use were significantly associated, but within caffeine users alcohol was associated with less frequent heavy caffeine consumption among smokers. In future studies, the measurement of plasma caffeine levels will help both to better define heavy caffeine intake and to control for smoking pharmacokinetic effects.

Adolescent↗
PubMed2006

Smoking is associated with schizophrenia, but not with mood disorders, within a population with low smoking rates: a matched case-control study in Bucaramanga, Colombia.

When comparing current smoking in schizophrenia patients versus the general population, the average odds ratio (OR) was 5.3 in a meta-analysis of 42 studies from 20 nations. Limited tobacco access can eliminate this strong association in some nations. Out of the 42 ORs, 37 were significantly higher than 1. Of the 5 non-significant ORs, three came from Colombian studies comparing current smoking prevalences in schizophrenia versus those in the general population (18%). However, the 3 ORs were not adjusted for confounders. We hypothesized that the association between schizophrenia and smoking is so strong that it can be detected in populations with limited access to smoking after carefully controlling for confounders. Of the three Colombian studies, one included 73 schizophrenia patients (DSM-IV schizophrenia or schizoaffective disorder) and 111 patients with mood disorders (DSM-IV bipolar or major depressive disorders). The current study matched each of these patients with 2 controls from the general population and performed more sophisticated statistical analyses. Prevalences of current smoking were 26% for schizophrenia patients and 10% for their matched controls (adjusted Mantel-Haenszel OR=3.1, 95% CI, 1.4-6.8), and 7% for patients with mood disorders and 12% for their matched controls (adjusted Mantel-Haenszel OR=0.62; CI, 0.28-1.4). The previously observed lack of association between schizophrenia and current smoking was due to lack of control of important confounding variables because of the absence of a control group. This re-analysis, which used a careful matching that controlled for confounders, suggests that the association between schizophrenia and smoking behaviors can stand in populations with low monetary income and low smoking rates. This study also suggests that the association between severe mood disorders (bipolar and major depression) and smoking is not as strong as that observed between schizophrenia and smoking, and may not be observable in countries where people have limited economic resources.

Adult↗
PubMed2006

Death caused by myocarditis in Wayne County, Michigan: a 9-year retrospective study.

This paper reviews 72 cases of death caused by myocarditis between the years 1996 and 2004, autopsied at the Office of the Wayne County Medical Examiner in Michigan. Myocarditis as a cause of sudden and unexpected death represented 1.3% of all natural deaths in Wayne County during said period. The year 1999 contained the highest number of deaths of this cause (18), where the average number of myocarditis deaths was 8 per year for this 9-year span. In this study, each case was reviewed based on information gathered from investigative, autopsy, and toxicology reports. Significantly, 58% of these cases were male, and 63.4% were African American. Myocarditis caused death in every age group between 7 months and 67 years, but adults between the ages of 19 and 67 were most significantly affected (75%). Flu and/or cold were the most common symptoms experienced in the days directly proceeding death (28%), followed by shortness of breath (17%) and sudden collapse (15%). Sixty-nine percent of these 72 cases were pronounced dead after ACLS (advanced cardiac life support) protocol by emergency medical services or hospital attendants. Cardiomegaly was observed in 24 cases of adults aged 19 or older (54%), and flabby/soft myocardial tissue was observed grossly in 16% of all 72 cases.

Adolescent↗
PubMed2006

Probable association between ziprasidone and worsening hypertension.

According to premarketing studies, at least 1% of ziprasidone-treated patients exhibited hypertension; however, this figure is not necessarily attributable to the drug. A PubMed/MEDLINE search yielded no articles describing hypertension as a possible adverse event associated with oral ziprasidone therapy. We describe a 53-year-old African-American woman with hypertension and schizophrenia whose blood pressure increased during ziprasidone therapy. She experienced no similar blood pressure increases during therapy with four other atypical antipsychotics. Her mean systolic blood pressure during ziprasidone treatment (158 mm Hg) was significantly higher than before (141 mm Hg) and after (135 mm Hg) treatment. Also, her mean diastolic blood pressure during ziprasidone treatment (88 mm Hg) was significantly higher than after treatment (79 mm Hg). Linear regression analysis demonstrated that the patient's systolic blood pressure increased significantly with ziprasidone dose (regression coefficient [B] = 0.22 mm Hg x day/mg, 95% confidence interval 0.10-0.34, p=0.001). Thus, after adjusting for the effect of antihypertensive doses, an increase of 40 mg/day in ziprasidone yielded an increase of 8.8 mm Hg in systolic blood pressure. For unknown (perhaps genetic) reasons, this patient may have been particularly sensitive to ziprasidone. Clinicians prescribing ziprasidone in patients with hypertension should be aware that their hypertension could worsen with the addition of ziprasidone. If this occurs, replacement of ziprasidone with a different antipsychotic should be considered.

Antipsychotic Agents↗
PubMed2006

Identification and management of Abdominal Compartment Syndrome in the Pediatric Intensive Care Unit.

OBJECTIVE: Asses if Abdominal Compartment Syndrome (ACS) increases the morbidity and mortality of the Pediatric Intensive Care Unit patients and if early recognition and intervention with decompressive therapy will alter outcome and decrease mortality. SETTING: Pediatric Intensive Care Unit of the University Pediatric Hospital-UPR. PATIENTS: All patients admitted to the PICU from July 1, 1999 to June 30, 2002 were enrolled in the study. Those having a distended and/or tense abdomen on physical examination were identified at risk for intra-abdominal hypertension (IAH). IAH was diagnosed if the intra-abdominal pressure (IAP) was above 10 mmHg and with ACS if the IAH was accompanied by: hemodynamic instability, oliguria or anuria, metabolic acidosis and respiratory deterioration. MEASUREMENTS AND MAIN RESULTS: 1052 patients were admitted to PICU. Ten patients with evidence of ACS were identified with an incidence of 0.9%. Ages ranged from 6 weeks to 12.3 years. Peak intravesical pressure measurements ranged from 17 to 39 mmHg. Inspiratory pressure was raised from a mean of 21.2 to 32.0 cmH2O. The PCO2 increased from a mean of 35.1 to 63 torr and the pH decreased from a mean of 7.40 to 7.12. Overall mortality was 40% for this patient population. CONCLUSIONS: The outcome of pediatric critical care patients depends on multiple variables. Now there is evidence that in a select group of patients IAH and ACS play a significant role in their morbidity and mortality. This makes it mandatory for clinicians taking care of this population to be increasingly aware of this condition.

Abdomen↗
PubMed2005

A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors.

A meta-analysis of worldwide studies, found by a 10-year literature follow-up and/or by searching PubMed, was performed. Forty-two studies across 20 nations consistently demonstrated an association between schizophrenia and current smoking (weighted average odds ratio, OR=5.9; 95% confidence interval, CI 4.9--5.7). In 32 male studies across 18 nations, the weighted average OR was 7.2 (CI, 6.1--8.3). In 25 female studies across 15 nations, the weighted average OR was 3.3 (CI, 3.0--3.6). The association between schizophrenia and current smoking remained after using severe mentally ill controls (18 studies across 9 countries, weighted average OR was 1.9, CI 1.7--2.1) and controlling for other variables (3 studies, adjusted ORs ranged 2-3). Heavy smoking (6 studies across 4 countries, ORs ranged 1.9--6.4) and high nicotine dependence were more frequent in smokers with schizophrenia versus the general population. There was no consistent evidence that heavy smoking or high nicotine dependence was more frequent in smokers with schizophrenia versus severe mentally ill controls. Cessation rates were lower in schizophrenia smokers versus the general population. Schizophrenia patients had a higher prevalence of ever smoking than the general population (9 studies across 6 countries, weighted average OR=3.1, CI 2.4--3.8) and than severe mentally ill patients (5 studies across 5 countries, OR=2.0, CI 1.6--2.4). Moreover, in two studies adjusting for confounders schizophrenia patients had an increased risk of starting daily smoking than controls. Thus, people who are going to develop schizophrenia have risk factors that make them more vulnerable to start smoking.

Comorbidity↗
PubMed2005

Smoking initiation and schizophrenia: a replication study in a Spanish sample.

In a prior US study, schizophrenia vulnerability was associated with higher risk of initiating daily smoking after 20 years of age. A survival analysis of onset age of daily smoking compared 290 controls with 250 consecutive DSM-IV schizophrenia patients from outpatient facilities at an urban catchment area in Spain. After controlling for gender and education, the cumulative hazard curves for smoking initiation age of controls and schizophrenia patients were significantly different. After age 20, smoking initiation rates were higher in all schizophrenia patients (and in 107 schizophrenia patients who started daily smoking at least 5 years before illness onset).

Adult↗
PubMed2005

Plasma clozapine concentration coefficients of variation in a long-term study.

Kurz et al. conducted the first study of the intra-individual variability of clozapine plasma concentrations but did not take into account the effect of smoking and co-medication. As patients were receiving varying doses, Kurz et al. standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients, the mean coefficient of variation (CV) was 53% (S.D. = 21). In this new study, plasma clozapine and norclozapine concentrations were measured every 2 weeks in 47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind clozapine trials under controlled conditions (stable smoking, limited co-medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day, the respective mean CVs for plasma clozapine concentrations were 23% (S.D. = 14), 19% (S.D.= 11) and 18% (S.D. = 8). For the combined concentrations of clozapine and norclozapine, the respective mean CVs were 20% (S.D. = 13), 16% (S.D. = 9) and 15% (S.D. = 7). Under 100 mg/day, the mean CV for clozapine concentrations was significantly higher for heavy smokers than non-heavy smokers (32%, S.D. = 3 vs. 19%, S.D. = 8) (p = 0.03). Studies of CVs in other environments are needed. Clozapine CVs may be important in order to understand the importance of variations around the therapeutic range and to interpret drug interactions above the usual noise of measuring plasma concentrations.

Adult↗
PubMed2005

Acquisition of luteolytic capacity involves differential regulation by prostaglandin F2alpha of genes involved in progesterone biosynthesis in the porcine corpus luteum.

Luteolytic capacity is defined as the ability of corpora lutea (CL) to undergo luteolysis after prostaglandin (PG) F2alpha treatment. The mechanisms causing acquisition of luteolytic capacity are not yet identified but CL without luteolytic capacity have PGF2alpha receptors and respond to PGF2alpha with some changes in gene expression. Inhibition of progesterone biosynthesis is a key feature of luteolysis and therefore we postulated that genes involved in progesterone biosynthesis would be regulated by PGF2alpha differently in CL with or without luteolytic capacity. Gilts on day 9 after estrus (lack luteolytic capacity) or day 17 of pseudopregnancy (with luteolytic capacity) were treated with saline or a PGF2alpha analog (cloprostenol) and CL were collected 0.5 (Experiment I) or 10 h (Experiment II) later. In Experiment III, large luteal cells from CL on day 9 or 17 were cultured for 1, 12 and 24h with or without PGF2alpha. PGF2alpha decreased LDL receptor mRNA (27%), steroidogenic acute regulatory protein (StAR) mRNA (41%), StAR protein (75%), LH receptor mRNA (55%), and LH receptor protein (45%) at 10 h after treatment in day 17 but not day 9 CL. PGF2alpha increased DAX-1 mRNA at 0.5 h (43%) and 10 h (46%) after PGF2alpha in day 17 but not day 9 CL but decreased 3betaHSD mRNA ( approximately 20% at 10 h) in both days 9 and 17 CL. In vitro, PGF2alpha decreased StAR mRNA at 12 h only in day 17 luteal cells; however, continuous treatment with PGF2alpha for 24 h decreased StAR mRNA in both days 9 and 17 luteal cells. Thus, luteolytic capacity involves a critical change in responsiveness of DAX-1, StAR, and LH receptor to PGF2alpha that results in inhibition of luteal progesterone biosynthesis.

Animals↗
PubMed2005

Does clozapine decrease smoking?

McEvoy et al.'s study in 1999, which used cotinine levels but had limited power, suggested that clozapine treatment may be associated with a mild smoking decrease (particularly when plasma clozapine levels are > 150 ng/ml). Some naturalistic studies also suggest that clozapine treatment may be associated with a mild smoking decrease. The present study included 38 schizophrenic daily smokers from a double-blind clozapine trial. Five analyses were tested for significant decreases in plasma cotinine levels from a haloperidol baseline to: (1) the end of clozapine trials regarding clozapine doses (100, 300 or 600 mg/day), (2) the end of the clozapine trial where the highest plasma clozapine level was achieved, (3) the end of the clozapine trial where a clozapine level in the 150-450 ng/ml range was achieved, (4) the end of the first clozapine trial regardless of clozapine dose, and (5) the end of the last clozapine trial in the study. The first and straightforward analysis by dose showed no clozapine effects on smoking. The second and the third analyses (an attempt to mimic the design by McEvoy et al. [McEvoy, J.P., Freudenreich, O., Wilson, W.H., 1999. Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol. Psychiat. 46, 125-129.]) also indicated that there was not a significant effect of clozapine on smoking. The fourth and five analyses were also negative. None of the five analyses in our clozapine trial demonstrated that clozapine had major effects on smoking. This study cannot rule out that in some subjects, clozapine treatment may be associated with a small decrease in smoking. New prospective longitudinal studies using repeated cotinine and clozapine levels are needed to explore whether clozapine may reduce smoking in some patients.

Adult↗
PubMed2005

A brief measure of high nicotine dependence for busy clinicians and large epidemiological surveys.

OBJECTIVE: It is important to perform a routine screening of nicotine dependence in psychiatric patients. The Fagerstrom Test for Nicotine Dependence (FTND) is a widely used six-item questionnaire. The Heavy Smoking Index (HSI) is a briefer measure including only two FTND items (time to first cigarette of day and number of daily cigarettes). In a prior study comparing HSI with FTND, a high HSI (score > or = 4) was a good and briefer alternative for detecting high nicotine dependence. The goals of this study were: (i) to compare the effectiveness of the HSI with the effectiveness of Items 1 and 4 alone for the screening of high nicotine dependence; (ii) to investigate the optimality of 4 as a cut-off score for the HSI so that the HSI can be used as a binary indicator of high nicotine dependence; and (iii) to compare the sensitivity and specificity of four indexes of high nicotine dependence, namely 'High HSI', 'Very Early Smoking', 'Heavy Smoking' and 'High in Either Item'. METHOD: The FTND was administered to 819 current daily smokers from a general population survey. As in a prior study, an FTND score > or = 6 was considered the reference or 'gold standard' test for detecting high nicotine dependence. Receiver-operating characteristic analyses were performed. RESULTS: This new study using more sophisticated statistical methodology verified that a cut-off of 4 for the HSI is appropriate and that the 'high' HSI has good sensitivity and specificity even across different population subclassifications. CONCLUSIONS: With four questions (smoking, daily smoking, time to first cigarette of day and number of daily cigarettes) and minimal calculations, it may be possible to screen whether a smoker has high nicotine dependence. If other studies in other populations and settings verify this finding, this brief measure might be an ideal screening instrument for busy clinicians, epidemiologists developing questionnaires for health surveys and psychiatric researchers.

Adolescent↗
PubMed2005

Movement, toxicity, and persistence of imidacloprid in seedling Tabasco pepper infested with Myzus persicae (Hemiptera: Aphididae).

Application of imidacloprid to the soil in which Tabasco pepper, Capsicum frutescens L., seedlings were growing was highly effective against the green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae). In just 48 h after the soil drench, aphid numbers on treated plants declined from 292.1 to 33.0 per plant, a reduction of 89%. By 72 and 96 h after the application, the reductions were 97 and 100%, respectively. Reductions in green peach aphid numbers also indicated that imidacloprid readily moved throughout the Tabasco pepper plant. Although, initial green peach aphid reductions at 24 and 48 h after imidacloprid application to soil, were greater on the lower leaves than on the upper leaves, by 72 h toxicity was high throughout the plant. At 48 h, overall green peach aphid reduction on seedlings grown in wet soil was significantly higher than that on plants growing in the drier soil. Regardless of soil moisture or leaf location, no live green peach aphids were detected on treated seedlings after 96 h. After the initial uptake period, toxicity to green peach aphid remained high for 5 wk. Under Tabasco pepper production conditions in Central America, the greatest need for aphid management is just after transplanting. Imidacloprid soil drenches before transplanting should offer the Tabasco pepper producer an extended period of aphid-free production.

Animals↗
PubMed2005

Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions.

BACKGROUND: Smoking may have a beneficial effect on either schizophrenic symptoms or antipsychotic side-effects, but studies are hampered by the lack of control of confounding factors. AIMS: To explore the self-medication hypothesis in a large sample of stable out-patients with schizophrenia. METHOD: Symptoms, assessed with the Positive and Negative Syndrome Scale (PANSS), and number of hospitalisations were compared in 250 out-patients with DSM-IV schizophrenia classified into three categories: highly dependent smokers, mildly dependent smokers and non-smokers. Log-linear analysis was used to control for potential confounding and interacting variables. RESULTS: High PANSS total scores and positive symptoms were less frequent in mildly dependent smokers than in non-smokers or highly dependent smokers. The highly dependent smokers had the worst outcome. CONCLUSIONS: The data do not generally support the self-medication hypothesis but rather suggest a complex interaction between nicotine dependence and nicotine dependence and schizophrenic symptoms.

Adult↗
PubMed2005

Obesity and associated complications in patients with severe mental illnesses: a cross-sectional survey.

BACKGROUND: This naturalistic cross-sectional survey of patients with severe mental illnesses explores the association between important variables and obesity, extreme obesity, diabetes mellitus type 2, hypertension, and hyperlipidemia in the clinical environment. METHOD: Weight and height were obtained from 560 patients with severe mental illnesses (including DSM-IV schizophrenia, schizoaffective disorder, bipolar disorder, and major depressive disorder) at central Kentucky inpatient and outpatient facilities to estimate their body mass index (BMI). Chart diagnoses of diabetes mellitus, hypertension, and hyperlipidemia were obtained. RESULTS: When comparing the patients with severe mental illnesses with Kentucky adults from the general population, the odds ratio (OR) of obesity (BMI > or = 30 kg/m(2)) was 2.6 (95% confidence interval [CI] = 2.2 to 3.0), and the OR of diabetes mellitus was 2.9 (95% CI = 2.3 to 3.6). Female gender, African American race, early start of psychiatric medication, and long psychiatric medication duration were significantly associated with obesity. Current alcohol and nicotine use exhibited significant ORs of obesity lower than 1, particularly in males. Obesity was closely associated with hypertension, type 2 diabetes mellitus, and hyperlipidemia. These complications were closely associated with each other and may indicate a further progression of obesity after aging. CONCLUSIONS: These results suggest a complex pattern of variables that may influence the development of obesity and its complications in patients with severe mental illnesses, but they need replication. The major factors associated with obesity appear to be a long-term illness or treatment duration and substance use. The former may be more important in females, while the latter may be more important in males. Clinical diagnoses (schizophrenic or mood disorders) or current treatment did not appear to be fundamental factors.

Adult↗