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Biomedical subjects

Bruce Alexander

Publications and source records attributed to Bruce Alexander.

13 recordsLinked to original sources

Canine visceral leishmaniasis: relationships between clinical status, humoral immune response, haematology and Lutzomyia (Lutzomyia) longipalpis infectivity.

The main source of Leishmania infantum infection in humans is a naturally infected dog. This study reports on the infectivity to phlebotomine sandflies (Lutzomyia longipalpis) of serologically positive mongrel dogs that differed in clinical status, haematology and humoral responses to immunoglobulin (Ig) G(T) (total anti-Leishmania IgG), IgG(1) and IgG(2) subclasses of antibody to crude antigen of L. infantum. Forty-five female L. longipalpis were allowed to feed directly on the ears of dogs classified as asymptomatic, oligosymptomatic or symptomatic before being dissected five days later. Promastigotes were detected in 88% of the dissected sandflies. The highest rate of infectivity to sandflies was found in symptomatic dogs, followed by oligosymptomatic and asymptomatic animals. The results suggest that dogs naturally infected with L. infantum with higher total IgG and IgG(2) concentrations and lower haematocrit levels were able to infect the highest proportion of L. longipalpis. No correlation was observed between anaemia and the intensity of clinical signs. Symptomatic dogs presented the highest infection rate and intensity of infection.

Animals↗

Risk of mortality associated with antipsychotic and other neuropsychiatric drugs in pneumonia patients.

OBJECTIVE: To evaluate the use of typical and atypical antipsychotic medications and associated in-hospital mortality in a group of Veterans Administration (VA) patients with pneumonia. METHOD: Our cohort consisted of 14,057 VA patients admitted for pneumonia in fiscal year (FY) 2003. Exposure to typical and atypical antipsychotics and other neuropsychiatric drugs was based on a prescription within 120 days preceding admission. Multivariate models determined the odds of mortality associated with each drug class and risk adjusted for comorbidity, admission source, demographic factors, and concurrent mental health conditions. The referent group for each analysis was pneumonia patients not receiving neuropsychiatric drugs. RESULTS: In adjusted analyses, the odds of in-hospital mortality for VA patients admitted with pneumonia was higher for recent exposure to typical antipsychotics (OR = 1.51, 95% CI = 1.04-2.19; P = 0.03) when compared to patients not receiving neuropsychiatric medications. Patients exposed to atypical antipsychotics (OR = 1.20, 95% CI = 0.96-1.50, P = .10), tricyclic antidepressants (OR = 1.20, 95% CI = 0.44-1.55; P = 0.15), other antidepressants (OR = 1.07, 95% CI = 0.93-1.23; P = 0.37), or mood stabilizers (OR = 0.91, 95% CI = 0.73-1.14; P = 0.41) had no significant difference in in-hospital mortality. CONCLUSION: In spite of recent safety concerns for atypical antipsychotics, we found no increased risk of mortality in acutely ill pneumonia patients. Rather, we found a higher adjusted mortality rate for patients taking typical antipsychotics. The contrasting mortality risks for patients taking typical and atypical antipsychotics may represent unmeasured severity of illness or comorbidity. Regardless, any antipsychotics should be used with caution and the efficacy and safety of alternative agents should be considered.

Aged↗

Rates of in vivo methylation of desipramine and nortriptyline.

Routine monitoring of an 81-year-old man receiving treatment with nortriptyline for generalized anxiety disorder and depression revealed plasma concentrations of both amitriptyline and nortriptyline. In humans, the tricyclic antidepressant (TCA) tertiary amines imipramine and amitriptyline are typically metabolized by demethylation to the secondary active metabolites desipramine and nortriptyline, respectively. However, to our knowledge, methylation of secondary amine TCAs has been reported in only one case report of nortriptyline overdose and in two studies involving desipramine. In a retrospective analysis of patients from five Veterans Affairs medical centers, the rate of methylation of desipramine and nortriptyline was 8.9 % (five of 56 patients) and 14.6% (36 of 247), respectively. Possible explanations for methylation include genetic polymorphisms in cytochrome P450 metabolizing enzymes, polymorphism of amine N-methyltransferase enzyme, drug-drug interactions, smoking, and alcohol consumption. However, the mechanism by which methylation occurs is unclear and warrants further investigation. Awareness of the phenomenon could help in discouraging repeated laboratory tests and unnecessary adjustments of drug therapies, resulting in cost savings and better patient outcomes.

Aged, 80 and over↗

Are insecticide-impregnated dog collars a feasible alternative to dog culling as a strategy for controlling canine visceral leishmaniasis in Brazil?

In a zoonotic visceral leishmaniasis (ZVL)-endemic area in Brazil, deltamethrin-impregnated collars (DMC) were fitted to 136 dogs for 5 months and significantly reduced the odds of increasing their anti-Leishmania antibody titer during this period by 50% (95% confidence interval 29-87%, P=0.01), as compared with a population of 97 uncollared dogs with pre-intervention prevalence within the same town. Mathematical modeling suggests that under typical Brazilian ZVL-endemic conditions, the epidemiological impact of community-wide DMC application should be greater than the currently practiced dog culling strategy, but that its impact will be dependent on collar coverage and loss rate. Both interventions should have a higher proportional impact in regions of lower endemicity, but the relative advantage of DMC over culling increases with transmission rate. Sensitivity analyses indicate that the impact of either intervention is not significantly affected by variation in the biology of the sandfly vector, but is greatly influenced by variation in dog mortality and serorecovery rates.

Animals↗

Osteoporosis screening and treatment in women with schizophrenia: a controlled study.

STUDY OBJECTIVE: As patients with a major psychiatric disorder such as schizophrenia generally are less likely to have their medical illnesses diagnosed and medically managed, we investigated whether osteoporosis screening, prevention management, and/or drug therapy (i.e., clinical services for osteoporosis) are provided consistently to both women with schizophrenia and those without the disease. DESIGN: Retrospective medical record review. SETTING: Three Midwest Veterans Affairs medical centers and clinics. PATIENTS: Forty-six women aged 45 years or older who had schizophrenia and 46 female control subjects who were frequency matched on age. MEASUREMENTS AND MAIN RESULTS: Twelve months of progress notes were reviewed for osteoporosis clinical services. In addition, smoking status, smoking cessation counseling, alcohol consumption, and fracture rates were compared between the groups. Overall, significantly fewer patients with schizophrenia (28 patients [61%]) received a clinical service for osteoporosis compared with the control group (37 patients [80%]). This difference was due to a significantly fewer number of patients with schizophrenia who received any osteoporosis agent (22 patients [48%]) compared with the control group (36 patients [78%]). Only 13 patients (28%) with schizophrenia received hormone replacement therapy compared with 25 control patients (54%). CONCLUSION: Women with schizophrenia in three Midwest Veterans Affairs medical centers did not receive the same level of osteoporosis care as that of age-matched control patients. This was primarily due to a lower utilization of osteoporosis agents, specifically hormone replacement therapy. Further research is necessary to determine the reason for this difference. Clinicians should be aware of medical management issues in patients with major psychiatric diagnoses and, specifically, osteoporosis care of women with schizophrenia.

Aged↗

Correlation of male genital filaments and female spermathecal ducts in New World sand flies of the Lutzomyia intermedia species complex (Diptera: Psychodidae, Phlebotominae).

The lengths of the male genital filaments and female spermathecal ducts were measured in phlebotomine sand flies of the Lutzomyia intermedia species complex and the ratios between these characters calculated. Ratios for L. intermedia s. s. from Northeast vs Southeast Brazil (Espírito Santo and Minas Gerais), Espírito Santo/Minas Gerais vs Rio de Janeiro/São Paulo and L. intermedia vs L. neivai were significantly different at P < 0.1, 0.05 and 0.01 respectively when compared using ANOVA. The spermathecal ducts and genital filaments of L. intermedia were significantly longer than those of L. neivai (P < 0.01) and could be used to differentiate these species. The taxonomic and biological significance of these differences is discussed.

Animals↗

Risk of melanoma among radiologic technologists in the United States.

Our study examines the risk of melanoma among medical radiation workers in the U.S. Radiologic Technologists (USRT) study. We evaluated 68,588 white radiologic technologists (78.8% female), certified during 1926-1982, who responded to a baseline questionnaire (1983-1989) and were free of cancer other than nonmelanoma skin at that time. Participants were followed through completion of a second questionnaire (1994-1998). We identified 207 cases, 193 subjects who reported first primary melanoma and 14 decedents with melanoma listed as an underlying or contributory cause of death. We examined risks of occupational radiation exposures using work history information on practices, procedures, and protective measures reported on the baseline questionnaire. Based on Cox proportional hazards regression, melanoma was significantly associated with established risk factors, including constitutional characteristics (skin tone, eye and hair color), personal history of nonmelanoma skin cancer, family history of melanoma and indicators of residential sunlight exposure. Melanoma risk was increased among those who first worked before 1950 (RR = 1.8, 95% CI = 0.6-5.5), particularly among those who worked 5 or more years before 1950 (RR = 2.4; 0.7-8.7; p (trend) for years worked before 1950 = 0.03), when radiation exposures were likely highest. Risk was also modestly elevated among technologists who did not customarily use a lead apron or shield when they first began working (RR = 1.4; 0.8-2.5). Clarifying the possible role of exposure to chronic ionizing radiation in melanoma is likely to require nested case-control studies within occupational cohorts, such as this one, which will assess individual radiation doses, and detailed information about sun exposure, sunburn history and skin susceptibility characteristics.

Adult↗

The taxonomic status of genetically divergent populations of Lutzomyia longipalpis (Diptera: Psychodidae) based on the distribution of mitochondrial and isozyme variation.

The sand fly, Lutzomyia longipalpis (Lutz & Neiva) reputedly is a complex of cryptic species; however, there is currently no consensus as to the number of species in the complex or their geographic distributions. We conducted phylogenetic analyses of 31 populations from throughout the species range, using seven isozyme loci and genes in the mitochondrial genome. Analyses of these two independent sets of markers were largely concordant and revealed four distinct clades that support the existence of four species. The four clades have distinct geographic ranges: (1) Brazil (Species A = Lu. longipalpis sensu stricto), (2) Laran (Species B = Lu. pseudolongipalpis), (3) cis-Andean (Species C), and (4) trans-Andean (Species D). The cis-Andean clade may be subdivided further into two groups, one in Colombia and one in northwestern Venezuela, but their taxonomic status remains unresolved. Knowledge that Lu. longipalpis is a complex of species may ultimately shed light on anomalies in the epidemiology of visceral leishmaniasis in the New World.

Animals↗

Transmission of Leishmania in coffee plantations of Minas Gerais, Brazil.

Transmission of Leishmania was studied in 27 coffee plantations in the Brazilian State of Minas Gerais. Eighteen females and six males (11.6% of the people tested), aged between 7-65 gave a positive response to the Montenegro skin test. Awareness of sand flies based on the ability of respondents to identify the insects using up to seven predetermined characteristics was significantly greater among inhabitants of houses occupied by at least one Mn+ve individual. Five species of phlebotomine sand fly, including three suspected Leishmania vectors, were collected within plantations under three different cultivation systems. Four of these species i.e., Lu. fischeri (Pinto 1926), Lu. migonei (França 1920), Lu. misionensis (Castro 1959) and Lutzomyia whitmani (Antunes Coutinho 1939) were collected in an organic plantation and the last of these was also present in the other two plantation types. The remaining species, Lu. intermedia (Lutz Neiva 1912), was collected in plantations under both the "adensado" and "convencional" systems. The results of this study indicate that transmission of Leishmania to man in coffee-growing areas of Minas Gerais may involve phlebotomine sand flies that inhabit plantations.

Adolescent↗

Rapid detection of Leishmania infantum infection in dogs: comparative study using an immunochromatographic dipstick test, enzyme-linked immunosorbent assay, and PCR.

Current zoonotic visceral leishmaniasis (ZVL) control programs in Brazil include the culling of Leishmania infantum-infected reservoir dogs, a strategy that has failed to prevent a rise of canine and human ZVL cases over the past decade. One of the main reasons this strategy has failed is because of a long delay between sample collection, sample analysis, and control implementation. A rapid, sensitive, and specific diagnostic tool would be highly desirable, because it would allow control interventions to be implemented in situ. We compared an immunochromatographic dipstick test to enzyme-linked immunosorbent assay (ELISA) and PCR for detecting L. infantum infections in dogs from an area of ZVL endemicity in Brazil. The dipstick test was shown to have 61 to 75% specificity and 72 to 77% sensitivity, compared to 100% specificity for both ELISA and PCR and 71 to 88% and 51 to 64% sensitivity for ELISA and PCR, respectively. Of the field samples tested, 92 of 175 (53%), 65 of 175 (37%), and 47 of 175 (27%) were positive by dipstick, ELISA, and PCR, respectively. The positive and negative predictive values for the tested dipstick were 58 to 77% and 75%, respectively. Efforts should be made to develop a more specific dipstick test for diagnosis of leishmaniasis, because they may ultimately prove more cost-effective than currently used diagnostic tests when used in mass-screening surveys.

Animals↗

Rabbit syndrome secondary to risperidone.

After taking risperidone for 4 months, a 38-year-old man with a major depressive disorder experienced rabbit syndrome. This uncommon extrapyramidal side effect is characterized by rhythmic movements of the mouth and may be caused by typical antipsychotics and risperidone secondary to blockade of dopamine D2 receptors. The syndrome, whose exact mechanism is unknown, responded to anticholinergic treatment in this patient. A literature review indicated that most recent cases have occurred as reactions to the atypical antipsychotic risperidone. Changing treatment to an atypical antipsychotic other than risperidone, such as olanzapine 10 mg/day, may lead to suppression or elimination of the syndrome.

Adult↗

Role of the domestic chicken (Gallus gallus) in the epidemiology of urban visceral leishmaniasis in Brazil.

Zoonotic visceral leishmaniasis (ZVL) is a serious public health problem in several Brazilian cities. Although the proximity of chicken houses is often cited as a risk factor in studies of urban ZVL, the role chickens play in the epidemiology of the disease has not been defined. Chickens attract both male and female sand flies (Lutzomyia longipalpis) but are unable to sustain Leishmania infections, and their presence may exert a zooprophylactic effect. We discuss environmental, physiologic, socioeconomic, and cultural factors related to chicken raising that could influence Le. infantum transmission in Brazilian cities and evaluate whether this practice significantly affects the risk of acquiring ZVL.

Animals↗

A regional comparison of developing diabetes among VA patients exposed to typical and atypical antipsychotics relative to corticosteroids and proton pump inhibitors.

BACKGROUND: Metabolic changes, including weight gain and onset of diabetes, have been associated with both systemic corticosteroid use and atypical antipsychotic drugs. The purpose of this study was to quantify and compare the risk of new-onset diabetes mellitus in a Veterans Affairs population receiving antipsychotics and corticosteroids, using persons taking proton pump inhibitors as a control group. METHODS: This study included data from subjects treated within Veterans Integrated Service Network 23 who had received an outpatient prescription in fiscal years (FY) 1999 or 2000 for a corticosteroid (CS), a proton pump inhibitor (PPI), a typical antipsychotic, or an atypical antipsychotic. Patients receiving prescriptions in more than one class were not excluded. Subjects were excluded if they had a documented diagnosis of diabetes either in the previous FY year (1998) or prior to their index prescription date. RESULTS: Thirteen percent of the population had a new diagnosis for diabetes during the two-year study. Cox-regression analysis using time dependent covariates determined a significantly higher risk of developing diabetes (RR = 1.21) in users of CS relative to PPIs. Demographic variables including age, race, gender, marital status, and VA financial classification as well as a marker for schizophrenia, were also included in the model. Comparison of both typical and atypical antipsychotics to PPIs found an increased but nonsignificant risk of developing diabetes (RR = 1.18 and RR = 1.19 respectively). CONCLUSIONS: The diabetogenic risk associated with atypical antipsychotics was found to be less than that of corticosteroids when compared to controls. Periodic monitoring of blood glucose should be considered with chronic use of an agent from either class.

Adrenal Cortex Hormones↗