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Biomedical subjects

J Valentine

Publications and source records attributed to J Valentine.

At least 19 recordsLinked to original sources
PubMed2006

Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration.

Workplace exposure to 1-bromopropane (1-BrP) can potentially occur during its use in spray adhesives, fats, waxes, and resins. 1-BrP may be used to replace ozone depleting solvents, resulting in an increase in its annual production in the US, which currently exceeds 1 million pounds. The potential for human exposure to 1-BrP and the reports of adverse effects associated with potential occupational exposure to high levels of 1-BrP have increased the need for the development of biomarkers of exposure and an improved understanding of 1-BrP metabolism and disposition. In this study, the factors influencing the disposition and biotransformation of 1-BrP were examined in male F344 rats and B6C3F1 mice following inhalation exposure (800 ppm) or intravenous administration (5, 20, and 100 mg/kg). [1,2,3-(13)C]1-BrP and [1-(14)C]1-BrP were administered to enable characterization of urinary metabolites using NMR spectroscopy, LC-MS/MS, and HPLC coupled radiochromatography. Exhaled breath volatile organic chemicals (VOC), exhaled CO(2), urine, feces, and tissues were collected for up to 48 h post-administration for determination of radioactivity distribution. Rats and mice exhaled a majority of the administered dose as either VOC (40-72%) or (14)CO(2) (10-30%). For rats, but not mice, the percentage of the dose exhaled as VOC increased between the mid ( approximately 50%) and high ( approximately 71%) dose groups; while the percentage of the dose exhaled as (14)CO(2) decreased (19 to 10%). The molar ratio of exhaled (14)CO(2) to total released bromide, which decreased as dose increased, demonstrated that the proportion of 1-BrP metabolized via oxidation relative to pathways dependent on glutathione conjugation is inversely proportional to dose in the rat. [(14)C]1-BrP equivalents were recovered in urine (13-17%, rats; 14-23% mice), feces (<2%), or retained in the tissues and carcass (<6%) of rats and mice administered i.v. 5 to 100 mg/kg [(14)C]1-BrP. Metabolites characterized in urine of rats and mice include N-acetyl-S-propylcysteine, N-acetyl-3-(propylsulfinyl)alanine, N-acetyl-S-(2-hydroxypropyl)cysteine, 1-bromo-2-hydroxypropane-O-glucuronide, N-acetyl-S-(2-oxopropyl)cysteine, and N-acetyl-3-[(2-oxopropyl)sulfinyl]alanine. These metabolites may be formed following oxidation of 1-bromopropane to 1-bromo-2-propanol and bromoacetone and following subsequent glutathione conjugation with either of these compounds. Rats pretreated with 1-aminobenzotriazole (ABT), a potent inhibitor of P450 excreted less in urine (down 30%), exhaled as (14)CO2 (down 80%), or retained in liver (down 90%), with a concomitant increase in radioactivity expired as VOC (up 52%). Following ABT pretreatment, rat urinary metabolites were reduced in number from 10 to 1, N-acetyl-S-propylcysteine, which accounted for >90% of the total urinary radioactivity in ABT pretreated rats. Together, these data demonstrate a role for cytochrome P450 and glutathione in the dose-dependent metabolism and disposition of 1-BrP in the rat.

Animals↗
PubMed2004

The quantification of paracetamol, paracetamol glucuronide and paracetamol sulphate in plasma and urine using a single high-performance liquid chromatography assay.

A range of analytical methods exist for the determination of paracetamol in biological fluids. However, to understand the fate of paracetamol and the effect of other drugs on its disposition in vivo, the major metabolites require quantification in urine and plasma. A method to simultaneously quantify paracetamol, paracetamol glucuronide (PG) and paracetamol sulphate (PS) in plasma and urine with superior sensitivity is therefore desired, especially if the volume of plasma available is low. A simple isocratic reverse phase high-performance liquid chromatography (HPLC) assay with spectrophotometric detection has been developed. The method, requiring only 100 microl of plasma and 50 microl of urine, utilizes a reversed-phase C18 column, a wavelength of 254 nm for detection and a mobile phase composed of potassium dihydrogen orthophosphate (0.1 M)-isopropanol-tetrahydrofuran (THF) (100:1.5:0.1, v/v/v) adjusted to pH 3.7 with phosphoric acid. The method is sensitive and linear in plasma within a concentration range from 0.4 to 200 microM for paracetamol, PG and PS. For PG and PS in urine, the method is sensitive and linear within a concentration range from 100 to 20,000 microM. Over these ranges, accuracy and precision were less than 12%. The assay has been used to measure concentrations of paracetamol and the two metabolites in plasma collected by finger-prick sampling and of the metabolites in urine from healthy volunteers administered a single oral dose of 1000 mg of paracetamol.

Acetaminophen↗
PubMed2001

Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences.

Mutation of BRCA2 causes familial early onset breast and ovarian cancer. BRCA2 has been suggested to be important for the maintenance of genome integrity and to have a role in DNA repair by homology- directed double-strand break (DSB) repair. By studying the repair of a specific induced chromosomal DSB we show that loss of Brca2 leads to a substantial increase in error-prone repair by homology-directed single-strand annealing and a reduction in DSB repair by conservative gene conversion. These data demonstrate that loss of Brca2 causes misrepair of chromosomal DSBs occurring between repeated sequences by stimulating use of an error-prone homologous recombination pathway. Furthermore, loss of Brca2 causes a large increase in genome-wide error-prone repair of both spontaneous DNA damage and mitomycin C-induced DNA cross-links at the expense of error-free repair by sister chromatid recombination. This provides insight into the mechanisms that induce genome instability in tumour cells lacking BRCA2.

Alleles↗
PubMed2001

Syphilis outbreak assessment.

BACKGROUND: Syphilis rates began to decline in 1991 and have decreased every year since. In 1998, 6,993 cases of primary and secondary syphilis were reported in the United States, for a national incidence of 2.6 cases per 100,000 population. Although syphilis rates are at an historic low, focal outbreaks still occur. On October 7, 1999, the Division of Sexually Transmitted Disease Prevention of the Centers for Disease Control and Prevention, in collaboration with federal and community partners, presented the National Plan for Elimination of Syphilis from the United States. One of the five key strategies of the plan is rapid outbreak response. METHODS: Methods for outbreak assessment and response were reviewed in the literature, synthesized, and adapted for use in syphilis outbreaks. RESULTS: Key elements of outbreak assessment and response are detection, surveillance data review, hypothesis generation, intervention development, and the evaluation of clinical, public health, and laboratory services. CONCLUSIONS: Outbreak response necessitates community participation and a coordinated interdisciplinary effort to determine social and behavioral contributors to the outbreak and to develop targeted interventions.

Centers for Disease Control and Prevention, U.S.↗
PubMed2001

The ascertainment and management of tuberculosis in Tayside, Scotland during 1993-94.

OBJECTIVE: To evaluate whether utilising a database of dispensed prescriptions for anti-tuberculous chemotherapy could improve case ascertainment compared to standard methods. A further objective was to assess whether cases were managed according to standard guidelines. DESIGN: Retrospective case note audit. SETTING: Tayside, Scotland SUBJECTS: Patients identified by conventional (i.e. SMRI diagnostic codes, notifications to the Health Board, microbiology and pathology reports) and the data base (MEMO) as potentially having tuberculosis and receiving treatment between 1st January 1993 and 31st December 1994. One hundred and ninety one potential cases were identified. One hundred and twenty two case notes were obtained for review. Eighty eight of these were initially thought to have tuberculosis and the results below refer to these 88 cases. RESULTS: MEMO identified 43 cases not found by conventional methods. Cases identified by MEMO were more likely to have been managed as outpatients and less likely to have positive microbiology than cases identified by conventional means. Only 26 cases were notified to the Health Board, including all smear positive cases. CONCLUSIONS: Notification of tuberculosis continues to be incomplete. Use of the MEMO system almost doubled case ascertainment. The absence of a firm diagnosis may lead to a reluctance to notify cases being treated as tuberculosis.

Antitubercular Agents↗
PubMed2000

Incidental splenic injury during abdominal vascular surgery: a case-controlled analysis.

BACKGROUND: The small but finite risk of postsplenectomy sepsis is generally regarded as a firm indication for splenic preservation after iatrogenic injury, especially in the young. But splenectomy may be preferable in patients who sustain splenic injuries during vascular operations because of the potential for continued bleeding associated with anticoagulation. The purpose of this study was to determine the perioperative morbidity of incidental splenectomy among patients undergoing abdominal vascular operations. STUDY DESIGN: We studied 17 patients who underwent incidental splenectomy at the time of abdominal vascular operations. Complete data collected on each subject included preoperative and postoperative blood counts, operative indications and details, transfusion requirements, length of hospital stay, and outcomes. Using age- and gender-matched case controls undergoing identical vascular operations from the same period, we evaluated the complication rate and outcomes of patients who underwent splenectomy for iatrogenic injuries of the spleen, versus those who did not sustain splenic injuries. RESULTS: The estimated prevalence of iatrogenic splenic injury during the study period was 0.5%. Mean operative time, estimated blood loss, and duration of mechanical ventilation tended to be greater in the splenectomy patients, but the differences did not achieve statistical significance. Splenorrhaphy was attempted in seven patients, but continued bleeding mandated spleen removal in all cases. Splenectomy patients had a higher transfusion requirement (p = 0.03) and a longer mean length of stay (p = 0.03) than controls. Compared with controls, there was a higher prevalence of infectious complications in the splenectomy patients (p = 0.015), but there was no difference in the prevalence of thromboembolic complications between groups. Two of the splenectomy patients died in the postoperative period from multisystem organ failure, and one died of a missed splenic injury. CONCLUSIONS: These data suggest that incidental splenectomy during abdominal vascular operations is associated with increased postoperative infectious complications and prolonged hospitalization.

Aged↗
PubMed1998

Gestational exposure to cocaine or pharmacologically related compounds: effects on behavior and striatal dopamine receptors.

Gestational cocaine (COC) exposure has been reported to alter behavior and possibly dopamine (DA) receptors. In this paper, we further examined the effects of prenatal COC (40 mg/kg, s.c.) on DA receptor binding and the behavioral response to quinpirole, a DA D2 receptor agonist. In an attempt to elucidate possible mechanisms of such effects, we exposed pregnant dams to specific reuptake blockers; fluoxetine 12.5 mg/kg, a serotonin reuptake blocker; desipramine 10 mg/kg, a norepinephrine reuptake blocker; GBR-12909 10 mg/kg, a DA reuptake blocker; or to a local anesthetic, lidocaine 40 mg/kg. Drugs were administered once daily over gestational days 8-20. Control dams were injected with saline (SAL) or pair-fed to the COC group. Quinpirole challenge was performed in the offspring on post natal day 19. Two pups per litter were injected (s.c.) with 0.03 or 0.09 mg/kg quinpirole-HCl on post-natal day 19. The remaining pups in each litter were sacrificed for analysis of striatal DA receptors. Results showed that only COC exposure altered the behavioral response to the quinpirole challenge by increasing quinpirole-induced stereotypy and motor activity relative to SAL controls. DA receptor analysis showed no alteration in K(D) or B(MAX) for striatal D1 or D2 sites in any group. These results suggest that prenatal COC exposure produces alterations in function of the D2 receptor complex which are not reflected in K(D) or B(MAX) and that these effects are not fully mimicked by exposure to specific monoamine reuptake blockers or a local anesthetic.

Animals↗
PubMed1998

Managerialism and active citizenship in Britain's reformed health service: power and community in an era of decentralisation.

The creation of a large managerial stratum within the British National Health Service in recent years has been one of the most striking characteristics of reforms intended to develop a more efficient and "business-like" service. An accompanying political rhetoric of decentralisation has cast local managerial autonomy as a means to gauge and respond more easily to the needs and preferences expressed by local communities. This article therefore reviews the growth of the new managerial stratum with particular regard to its emerging relationship with the local populations in whose name the organisational reforms have been wrought. The dominant political interpretation of this relationship--that the organisational reforms constitute a movement from leaden "bureaucratic" administration to more locally accountable and responsive managerial regimes--is then tested with regard to an in-depth study of two health authorities responsible for very different local populations. Results show that the role of local populations in influencing decisions and determining priorities is considerably less than inferred by the sustained political rhetoric in favour of the "local voices". Consideration of possible trends in the state and economy suggests however that this disjuncture may not be explicable solely in terms of the new managerial stratum maximising its influence or of central government retaining a high degree of control.

Community Health Services↗
PubMed1998

Predictive model of weapon carrying among urban high school students: results and validation.

OBJECTIVES: The purpose of this study was to identify the behavioral, psychosocial, and demographic predictors of self-reported weapon carrying among secondary school students who attend urban public schools. METHODS: Self-reported weapon carrying was measured in a schoolwide anonymous health survey conducted in two demographically comparable high schools in 1992, in Boston, Massachusetts. Indicators of self-perception, depression, stressful life events, and adolescent risk behaviors of substance use and sexual behavior, along with self-reported weapon carrying, were measured. The students in both schools were racially heterogeneous, with the majority of about 80% from black or Hispanic backgrounds. A predictive model was developed using a forward stepwise logistic regression model in one inner-city high school, and tested in a second high school. RESULTS: Self-reported lifetime weapon carrying was 32% overall. The major predictors of weapon carrying among urban secondary school students are a combination of demographic, psychosocial, behavioral, and school-related factors. This analysis indicates consistency in eight markers predictive of weapon carrying: lower age, male gender, regular marijuana use, sexual experience, having witnessed a crime, having skipped school, suicidal ideation, and having hit or "beat up" someone. Race parental education, and family composition were not significant predictors. Significant predictors of weapon carrying were marijuana use and sexual experience, each of which was consistently high in both schools. CONCLUSIONS: The model-building and validation presented in this study provide empirical evidence for three important conclusions. First, weapon carrying is associated with multiple and interrelated factors which include demographic, psychosocial, behavioral, and school-related characteristics of high school-age adolescents. Second, students with more risk factors are more likely to carry a weapon, suggesting that the variables are independent markers. Third, this study identified marijuana use and being sexually experienced as both highly predictive of weapon carrying. Implications of this study for prevention point to the need for comprehensive multidisciplinary services in high school that include mental health counseling as well as health education efforts aimed at behavior change.

Adolescent↗
PubMed1997

Expressed sequences from conidial, mycelial, and sexual stages of Neurospora crassa.

In the Neurospora Genome Project at the University of New Mexico, expressed sequence tags (ESTs) corresponding to three stages of the life cycle of the filamentous fungus Neurospora crassa are being analyzed. The results of a pilot project to identify expressed genes and determine their patterns of expression are presented. 1,865 partial complementary DNA (cDNA) sequences for 1,409 clones were determined using single-pass sequencing. Contig analysis allowed the identification of 838 unique ESTs and 156 ESTs present in multiple cDNA clones. For about 34% of the sequences, highly or moderately significant matches to sequences (of known and unknown function) in the NCBI database were detected. Approximately 56% of the ESTs showed no similarity to previously identified genes. Among genes with assigned function, about 43.3% were involved in metabolism, 32.9% in protein synthesis and 8.4% in RNA synthesis. Fewer were involved in defense (6%), cell signalling (3.4%), cell structure (3.4%) and cell division (2.6%).

Amino Acid Sequence↗
PubMed1997

Thyroid function in a population of children with attention deficit hyperactivity disorder.

OBJECTIVE: To determine the prevalence of thyroid hormone abnormalities and generalized resistance to thyroid hormone in a population of children with attention deficit hyperactivity disorder (ADHD) as compared to reference ranges determined from a control population and hence to determine if routine thyroid hormone screening in children with non-familial ADHD is indicated. METHOD: Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed. RESULTS: The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%. CONCLUSION: Routine thyroid hormone screening is not indicated in children with non-familial ADHD.

Adolescent↗
PubMed1997

Increase of manganese superoxide dismutase, but not of Cu/Zn-SOD, in experimental optic neuritis.

PURPOSE: To evaluate the role of manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu/Zn-SOD) in cellular protection of the optic nerve against the oxidative injury that contributes to demyelination in experimental allergic encephalomyelitis (EAE). METHODS: Immunocytochemistry for Mn-SOD and Cu/Zn-SOD and ultracytochemical localization of hydrogen peroxide (H2O2) were performed on the optic nerves of guinea pigs with EAE and normal guinea pigs. Cell-specific enzyme expression of SOD was quantitated by computerized morphometric analysis. RESULTS: Light microscopy showed a perivascular distribution of Mn-SOD-positive cells in the optic nerves of animals with EAE. Electron microscopy showed that the Mn-SOD immunogold was confined exclusively to mitochondria, whereas Cu/Zn-SOD immunogold was found in the cytoplasmic matrix and nucleus of cells of the optic nerve in both animals with EAE and normal animals. Results of quantitative analysis of the optic nerves of animals with EAE showed an 8-fold increase in Mn-SOD immunogold in astroglial cells and a 13-fold increase in microglial/phagocytic cells in comparison with that of normal animals. Increases in Mn-SOD immunogold were contiguous to H2O2-derived reaction product. No increases in Cu/Zn-SOD immunogold were detected in EAE. CONCLUSIONS: Increases in Mn-SOD activity in astroglial cells and microglial/phagocytic cells may contribute to the relative sparing of these cells from injury in EAE, whereas the low level of Mn-SOD in oligodendroglial cells and axons may increase their vulnerability to the effects of superoxide-induced oxidative injury that results in demyelination.

Animals↗
PubMed1996

Phase I trial of intravenous carboplatin added to oral etoposide and oral cyclophosphamide for stage IV non-small cell lung cancer.

The combination of oral etoposide and oral cyclophosphamide is an active and easily administered outpatient regimen for non-small cell lung cancer with leukopenia as the most common severe toxicity. To maintain ease of outpatient administration and to take advantage of a differing dose-limiting toxicity, we attempted to add escalating doses of intravenous carboplatin to full-dose oral etoposide and oral cyclophosphamide for chemotherapy-naive patients with Stage IV non-small cell lung cancer. The first 4 patients received etoposide and cyclophosphamide (each at 50 mg PO BID Days 1-12 every 28 days) with intravenous carboplatin on Day 1 at a dose calculated by the Calvert formula to achieve AUC 4. With this regimen dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was noted. An additional 3 patients therefore received etoposide and cyclophosphamide at a 25% reduced dose (each at 50 mg PO BID Days 1-9 every 28 days) with intravenous carboplatin on Day 1 at a dose calculated to achieve AUC 4. Dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was again noted. One patient achieved a partial response maintained for 6 months. However potentiation of leukopenia/granulocytopenia by carboplatin prevents full-dose use of either cyclophosphamide and etoposide or of carboplatin in this regimen.

Administration, Oral↗
PubMed1996

National trends in the use of stimulant medication for attention deficit hyperactivity disorder.

OBJECTIVE: To document the use of stimulant medication in the different states and territories of Australia in 1993 and trends in use of stimulant medication in Western Australia and New South Wales from 1988 to 1993. METHODOLOGY: Health authorities in the states and territories of Australia were contacted and requested to provided data on total numbers, patient gender, date of birth, postcode and type of stimulant medication prescribed to estimate the prevalence of use of stimulant medication in Australia. RESULTS: Despite variation in the data obtained from each health authority there is a significant difference in the rates of use of stimulant medication between states and territories in Australia, and a significant increase in use between 1988 and 1993 in Western Australia and New South Wales. CONCLUSIONS: These trends should continue to be closely monitored and the possibility of establishing national prescription guidelines considered.

Adolescent↗