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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 397 records · Page 22Linked to original sources
PubMed1998

The effect of divergent selection for total plasma phosphorus in Japanese quail on fearfulness and selected blood and heart parameters.

A selection experiment utilizing Japanese quail was initiated to study the genetic relationship of growth and reproduction traits. In this study, lines were selected for increased (HP line) and decreased (LP line) total plasma phosphorus at the beginning of lay. The HP and LP lines were derived from a randombred control population (R1 line) that was maintained with the selected lines to remove environmental variation over generations. During the course of selection, it was observed that blood from HP line females was more viscous than that of the LP and R1 females. In later generations of selection, mortality of females during a 120-d egg production period was higher in the HP line than in the LP and R1 lines. The purpose of this experiment was to identify possible factors contributing to the increased mortality in the HP line. Fearfulness, as measured by tonic immobility, was greater in the HP and LP lines than in the R1 line. Indirect blood pressure measurements were made near the beginning and near the end of the 120-d egg production period. No significant line differences were observed in either measurement. Weight of the heart at the end of the laying period was higher in the HP and LP lines than in the R1 line. Histological study of the hearts of the HP and R1 lines indicated significant increases in the HP line in collagen content of the coronary arteries and in myocardial fibrosis. The data suggest that the increased mortality of females of the HP line relative to the R1 line during the laying period may be related to increased fearfulness and changes in the coronary structure leading to heart abnormalities.

Animals↗
PubMed1998

The effect of full-thickness abdominal wall burns sustained during childhood on subsequent childbearing ability.

The effect of full-thickness burns of the abdomen during childhood on subsequent pregnancy was evaluated. Eight hundred female pediatric patients treated for acute burns during a 14-year period (1975-1989) at the Shriners Burns Institute were reviewed. Through a combination of clinical follow-up, questionnaires, or phone interviews, data were obtained regarding the histories of 31 pregnancies in 19 patients who had required excision and skin grafting of > or = 50% of their abdominal wall during management of their acute burns. These patients sustained a mean burn size of 59.8% total body surface area (TBSA; range, 23-87%) with a mean full-thickness burn of 43.8% TBSA (range, 10-78%). The mean age at the time of burn was 7.6 years (range, 1.5-15 years). Normal rates of vaginal and cesarean section deliveries, prematurity, and infant mortality were observed in these 31 pregnancies. Despite a subjective sensation of increased tension on the scar in 25% of the patients, no interference with these patients carrying a full-term pregnancy directly attributable to the burn scar was identified. Follow-up and examination during the third trimester of pregnancy demonstrated how the burned and unburned portion of the abdominal wall accommodated the enlarged uterus. This review demonstrates that after extensive burns to the abdomen, which have been treated with excision and skin grafting during childhood, the scarred abdominal wall accommodates full-term pregnancy without the need for surgical release.

Abdominal Injuries↗
PubMed1998

Capsular calcification associated with silicone breast implants: incidence, determinants, and characterization.

Capsular calcification was present clinically in 64 of 404 silicone gel breast implant capsules (15.8%) analyzed from 1981 to 1996. It presented as white-gray plaques on the inner surface of capsules in 62 of 64 capsules, and as massive heterotopic ossification in 2 capsules. Chi-squared analysis confirmed that calcification was related to the generation of the implant (i.e., year of manufacture; p < 0.001). All 28 first-generation implants (1963-1972, with Dacron patches) were clinically intact and all demonstrated extensive calcification. Their mean duration in situ was 17.6 years (range, 14-28 years). Thirty-four of the 348 second-generation implants (9.8%; 1973-1987) were associated with capsular calcification. Their mean duration in situ was 16.0 years (range, 13-22 years). Because all first-generation implants demonstrated calcification, they were compared with the second-generation implants that had been in place for the same duration (>14 years). Only 42% of these 81 second-generation implants demonstrated calcification, compared with 100% of the first-generation implants (p < 0.001). Thus, thicker first-generation implants with Dacron patches are more likely to calcify and the effect is not entirely due to their longevity. None of the 28 third-generation implants (1987-1991) demonstrated calcification. Their mean duration in situ was 4.2 years (range, 2-7 years). For second-generation implants, calcification was related to duration in situ (p < 0.001). None of the 294 implants in place for less than 11 years were associated with significant clinical calcification. The percentages of capsules with calcification were 13 to 14 years, 33%; 15 to 16 years, 45%; and 17 to 22 years, 57%. Calcification with second-generation implants was not associated with patches on the envelopes. Of the 34 second-generation implants with calcification, only two had patches (composed of silicone, not Dacron). Among second-generation implants, calcification was related to implant integrity. Of implants in place for more than 12 years, 52.5% of those implants that were ruptured showed calcification, but only 10.0% of intact implants demonstrated calcification (p < 0.001). Seventeen of the 64 calcified capsules were examined histologically. In all of these specimens, calcification existed in two forms: globular aggregates on the surface of the capsule (adjacent to the implant) and actual bone formation within the fibrous tissue of the capsule. All calcified capsules demonstrated both globular aggregates and true bone formation regardless of the implant generation, duration in situ, or integrity. Ultrastructural analysis was performed on four capsules from 2 women who had received first-generation Dow Corning gel implants 24 and 28 years previously, and on 2 capsules from one woman who had received Heyer-Schulte gel implants 21 years previously. These capsules were analyzed according to distribution, density, mineral nature, crystal phases, and elements within crystals by electron microscopy, energy-dispersive X-ray spectrometry, and electron diffraction. These analyses confirmed two types of calcification, each with hydroxyapatite crystals. In areas of heterotopic bone, crystals 40 x 10 nm were deposited in an orderly fashion on collagen fibers. In contrast, in areas of globular aggregates, spherulitic aggregates of much larger crystals were present, without any relationship to the collagen. Titanium was demonstrated in capsules of first-generation implants at areas of attachment of the Dacron patches. The calcification associated with saline implants revealed only one form of crystal: agglomerates, which were adherent to the elastomeric shell of the implants. A hypothesis is presented to explain the differences in calcification deposition properties between silicone gel-filled and saline-filled breast implants.

Adult↗
PubMed1998

Cytokine gene therapy or infusion as treatment for solid human cancer.

In the induction of tissue-directed immune responses, cytokines tend to be released within the affected tissues. We used two strategies to expose tumor tissues to continuous high levels of cytokines: First, a vaccinia interleukin (IL)2 recombinant was injected directly intratumorally 3-weekly at 10(7) pfus/dose in six patients with the solid tumor malignant mesothelioma (MM). No virus excretion was detectable. At each cycle vaccinia-IL-2 mRNA (SQ [semi-quantitative] reverse transcription polymerase chain reaction) was maximal 24-72 h following injection reduced at 8 days and faded by 21 days. No tumor regression occurred. Second, based on the success of granulocyte macrophage colony-stimulating factor (GM-CSF) in gene transfer experiments, we conducted a study using continuous intratumoral GM-CSF infusion in eight patients with MM using a portable pump at doses of 10 micro/cg/24 h over 8 weeks. Systemic neutrophil agglutination and local catheter-related difficulties occurred. Two patients demonstrated tumor necrosis, one of whom had a marked progressive mononuclear cell infiltration of the tumor associated with a partial response (>50% reduction in tumor area). Murine studies using our MM model in CBA and BALB/C mice have demonstrated that B7-1 and allo-class I transfections induce strong tumor-specific cytotoxic T lymphocyte responses: GM-CSF, IL-12, and IL-2 induced mixed nonspecific plus specific responses, whereas B7-2 and class II transfections were not effective. We conclude that increased intratumoral cytokine concentrations can be generated using both gene transfer and cytokine infusion approaches; however, both have their limitations and, at this stage, have not produced dramatic antitumor effects in humans.

Cytokines↗
PubMed1998

Effect of ursodeoxycholic acid therapy on hepatic function in children with intrahepatic cholestatic liver disease.

BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to improve pruritus, alanine aminotransferase (ALT), and cholesterol levels in children with intrahepatic cholestatic liver disease. However, the effect of UDCA on quantitative tests of hepatic function in children is uncertain. METHODS: A 2.5-year, open label, crossover study, was designed to determine the effect of UDCA (15-20 mg/kg per day for 12 months, off for 6 months, and on again for 12 months) on clinical symptoms, biochemical test results, galactose and caffeine elimination half-lives (t1/2), and quantitative hepatic scintigraphy in 13 subjects aged 13.1 +/- 2.1 years (10 of whom completed the entire study), with intrahepatic cholestasis. RESULTS: Pruritus improved with UDCA in the 6 patients with pruritus on entry into the study. At 12 months, there was a significant decline in ALT, gamma-glutamyl transpeptidase, and plasma levels of copper and manganese, with no further decline in these levels at 24 months. There were no changes in bilirubin or cholylglycine levels. After therapy was discontinued at 12 months, UDCA was restarted within 1 month in 9 of 12 patients in response to a doubling of ALT (n = 6) or worsening pruritus (n = 3). Galactose t1/2 increased after 12 months, with no further increases after 24 months of UDCA therapy, whereas caffeine t1/2 did not change. There were no significant changes in hepatic scintigraphy throughout the study. CONCLUSIONS: These data suggest that although UDCA therapy improves pruritus and results in a reduction in ALT and gamma-glutamyl transpeptidase, UDCA therapy did not improve quantitative measures of hepatic function in children with intrahepatic cholestasis.

Adolescent↗
PubMed1998

The HIV Epidemiology Research Study, HIV Out-Patient Study, and the Spectrum of Disease Studies.

The Division of HIV/AIDS Prevention at the United States Centers for Disease Control (CDC) has several observational databases through which it collects individual level data that can be used to evaluate the spectrum of HIV-related diseases and the utilization of HIV-related health care services. The HIV Epidemiology Research Study (HERS) is a multisite, prospective cohort study of HIV-infected women and uninfected women reporting HIV risk behavior. By interview, clinical examination, specimen collection and storage, laboratory testing, and medical record abstraction. HERS is examining the manifestations, correlates and predictors of HIV disease in women. In addition to the basic visits, a variety of nested studies are under way and several more are planned. Three additional observational databases collect individual level data primarily through systematic medical record abstraction. The Adult Spectrum of Disease (ASD) Study and the Pediatric Spectrum of Disease (PSD) Study collect data from a national sample of hospital and clinic medical records. The ASD also has a supplementary interview administered to consenting patients with new AIDS diagnoses in a subset of their study sites. The HIV Out-Patient Study (HOPS) collects data from an electronic charting system on outpatient findings and clinical care for patients attending a national sample of infectious disease clinics.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Contribution of individual drugs to gingival overgrowth in adult and juvenile renal transplant patients treated with multiple therapy.

Drug regimens for transplantation often consist of multiple therapeutic agents and may result in drug-induced gingival overgrowth (DIGO). The aim of this study was to investigate the contribution of individual drugs in renal transplant patients. 147 adults (19-84 years) and 60 juveniles (3-18 years) were scored for DIGO and other clinical variables. Duration of treatment, dosage of drugs per kg body weight and serum cyclosporin levels were recorded. 44% of adults and 27% of children had DIGO. All patients were receiving prednisolone. More adults than children were administered cyclosporin, the reverse was true of azathioprine (p<0.01). Explanatory models were evaluated by stepwise ordinal polynomial logistic regression. Statistically significant explanation (p<0.05) of DIGO was afforded by prednisolone, nifedipine and azathioprine concentrations in adults and by cyclosporin, nifedipine and azathioprine concentrations in juveniles. Prednisolone and azathioprine were inversely related to the degree of DIGO. Plaque and irregularity scores, lip coverage and mouthbreathing status showed significant additional explanation in adults, replacing nifedipine and azathioprine in the final model. Irregularity was additionally explanatory in children, but no other clinical variables. A larger proportion of the variance of DIGO was explained by the available variables in children than in adults (pseudo r2=0.50 versus 0.25). The degree of DIGO in renal transplant patients is influenced by the dosage of a number of individual components of multiple drug therapy independently of the presence of local clinical factors.

Adolescent↗
PubMed1998

A nested-PCR-based schizodeme method for identifying Leishmania kinetoplast minicircle classes directly from clinical samples and its application to the study of the epidemiology of Leishmania tropica in Pakistan.

A nested PCR was developed to amplify the variable region of the kinetoplast minicircles of all Leishmania species which infect mammals. Each Leishmania parasite contains approximately 10,000 kinetoplast DNA minicircles, which are unequally distributed among approximately 10 minicircle classes. The PCR primers were designed to bind within the 120-bp conserved region which is common to all minicircle classes; the remaining approximately 600 bp of each minicircle is highly conserved within each minicircle class but highly divergent between classes. The nested PCR generated a strong signal from a minimum of 0.1 fg of Leishmania DNA. Restriction digests of the amplicons from the highest dilutions suggested that minicircles from only a limited number of minicircle classes had acted as template in the reaction. One PCR product was directly sequenced and found to be derived from only one minicircle class. Since the primers amplify all minicircle classes, this indicated that as little as 1/10 of one Leishmania parasite was present in the PCR template. This demonstrated that the nested PCR achieved very nearly the maximum theoretically possible sensitivity and is therefore a potentially useful method for diagnosis. The nested PCR was tested for sensitivity on 20 samples from patients from the Timargara refugee camp, Pakistan. Samples were collected by scraping out a small amount of tissue with a scalpel from an incision at the edge of the lesion; the tissue was smeared on one microscope slide and placed in a tube of 4 M guanidine thiocyanate, in which the sample was stable for at least 1 month. DNA for PCR was prepared by being bound to silica in the presence of 6 M guanidine thiocyanate; washed in guanidine thiocyanate, ethanol, and acetone; and eluted with 10 mM Tris-HCl. PCR products of the size expected for Leishmania tropica were obtained from 15 of the 20 samples in at least one of three replicate reactions. The negative samples were from lesions that had been treated with glucantime or were over 6 months old, in which parasites are frequently scanty. This test is now in routine use for the detection and identification of Leishmania parasites in our clinical laboratory. Fingerprints produced by restriction digests of the PCR products were defined as complex or simple. There were no reproducible differences between the complex restriction patterns of the kinetoplast DNA of any of the parasites from Timargara camp with HaeIII and HpaII. The simple fingerprints were very variable and were interpreted as being the product of PCR on a limited subset of minicircle classes, and consequently, it was thought that the variation was determined by the particular minicircle classes that had been represented in the template. The homogeneity of the complex fingerprints suggests that the present epidemic of cutaneous leishmaniasis in Timargara camp may be due to the spread of a single clone of L. tropica.

Animals↗
PubMed1998

Epidemiology of bicycle injury, head injury, and helmet use among children in British Columbia: a five year descriptive study. Canadian Hospitals Injury, Reporting and Prevention Program (CHIRPP).

OBJECTIVES AND METHODS: Data on 1462 injured bicyclists aged 1-19, obtained over a period of five years from the British Columbia Children's Hospital as part of a national emergency room based program in Canada, were analyzed to describe the epidemiology of injuries, helmet use, and the occurrence of head injuries before the enactment of a new mandatory helmet law. The odds ratio (OR) and 95% confidence interval (CI) were calculated for non-users compared with helmet users. RESULTS: Bicycle injuries comprised 4% of all injuries seen in the five year study period. The proportion of admissions was 12.7% among bicyclists, significantly higher than the 7.9% admissions of all 35,323 non-bicyclist children who were seen during the study period (OR = 1.96, CI = 1.44 to 1.99). Boys were injured more often than girls. The proportion of admissions for boys was 13.8% compared with 10.2% among girls (OR = 1.41, CI = 0.97 to 2.05). More than 70% of injured bicyclists reported no helmet use. The proportion of admissions of injured bicyclists who did not use helmets was always higher than the proportion of admissions of those who used helmets (OR = 2.23, CI = 1.39 to 3.62). Head and face injuries occurred more often among those who did not use helmets (OR = 1.55, CI = 1.18 to 2.04). However, there was no excess of minor head injuries among non-users (OR = 1.10, CI = 0.60 to 2.06). Of the 62 concussions, 57 occurred to non-helmet users (OR = 4.04, CI = 1.55 to 11.47). Most injuries occurred in the upper (46.4%) or lower extremities (32.4%). Dental injuries occurred slightly more often among helmet users compared with non-users but this excess was not statistically significant (OR = 1.29, CI = 0.76 to 2.20). CONCLUSION: The data indicate the need to control injuries by using helmets. A decrease in the number of head injuries and their severity is expected when bicycle helmet use becomes law in British Columbia.

Adolescent↗
PubMed1998

Relation between alpha, beta, and gamma human amiloride- sensitive epithelial Na+ channel mRNA levels and nasal epithelial potential difference in healthy men.

To analyze messenger RNA (mRNA) levels for the alpha, beta, and gamma subunits of the human amiloride-sensitive epithelial Na+ channel (hENaC) in respiratory epithelia, we developed a competitive quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) assay specific for each subunit, using two human respiratory epithelial-cell lines. We next determined the relation between hENaC mRNA levels and the biologic activity of the hENaC in the respiratory epithelium of eight normal men. The electrical potential difference (PD) between the epithelium of the inferior nasal turbinate and the subcutaneous space was measured, using control and amiloride (100 microM) solutions. QRT-PCR measurement of hENaC-subunit mRNAs and epithelial-specific cytokeratin 18 mRNA allowed us to normalize hENaC expression to epithelial-cell RNA. Respective values for alpha, beta, and gamma hENaC mRNA levels in epithelium obtained at the site of maximal PD were 39 +/- 4.0, 7.5 +/- 0.92, and 1.8 +/- 0.25 attomol/fmol cytokeratin mRNA, respectively. Respiratory epithelial PD exhibited a significant negative correlation with gamma hENaC (r2 = 0.72, p < 0.01), tended to increase with increasing alpha hENaC, and was unaffected by beta hENaC mRNA levels. Our results suggest that hENaC activity in vivo is influenced by expression of the gene for gamma hENaC. The assay used in the study provides a useful tool for evaluating Na+-channel expression in clinically relevant patient populations.

Adenocarcinoma, Papillary↗
PubMed1998

Mandibular advancement devices for the control of snoring.

Patients presenting with the complaint of antisocial snoring have very few options available to them of proven efficiency. Mandibular advancement devices worn intra-orally at night, have recently been shown in controlled trials to help mild to moderate obstructive sleep apnoea. However, there are no properly controlled studies with objective measurements on the use of such appliances for the management of antisocial snoring. Fifteen patients, already established on mandibular advancement devices for the control of snoring, were asked to participate in this study. They were studied over two nights, using a portable sleep monitoring device at home, both with and without their mandibular advancement devices in place (in randomized order). Snoring was measured using a surface throat microphone. In addition oxygen saturation and indirect beat to beat blood pressure were measured. The latter (using pulse transit time) provided an index of autonomic "arousals" and a measure of inspiratory effort. In nearly all of these highly selected patients the mandibular advancement devices reduced significantly the amount of snoring from a median of 193 to 20 snores x h(-1) (p<0.0001). In addition there was a reduction in respiratory effort, implying enlargement of the upper airway whilst wearing the appliance. These patients only represent those who were able to tolerate the appliance. With such clear evidence of their potential efficacy, and no suggestion from other studies of any harm, it would seem reasonable to introduce this approach into the management of antisocial snoring.

Adult↗
PubMed1998

Palliative care in chronic obstructive airways disease: a needs assessment.

The view that palliative care should move beyond cancer is widely endorsed, however, there remains a lack of clarity about the level at which this should occur. In order to target the palliative approach effectively, the value of more detailed and localized needs assessment becomes apparent. This paper provides evidence from a study commissioned by a department of public health, where the focus was the palliative care needs of an individual with chronic obstructive airways disease (COAD). Over a six-month period, 63 individuals in the district were interviewed about their experiences of living with COAD and the services utilized, using a combination of qualitative and quantitative research methods. The findings revealed a poor quality of life, relating to a high degree of social isolation and emotional distress, associated with low physical functioning and disability, and physical symptoms. Current service provision focused on acute exacerbations. Consequently, there is a need to manage the health and social care interface more effectively, with a shift in emphasis from reactive ad hoc provision, which is where the palliative approach to care could be best suited to meet the needs identified.

Aged↗
PubMed1998

Practice styles of US compared to UK neurologists.

OBJECTIVE: This study assessed variation between neurologists in the United States and United Kingdom in their diagnostic and treatment decisions for commonly encountered neurologic presentations, and identified explanatory factors for any observed variation. METHODS: All 210 consultant neurologists in the United Kingdom and a nationally representative sample of 595 US neurologists received mailed surveys containing three detailed clinical scenarios depicting patients with (1) a single unprovoked seizure occurring 3 days previously, (2) early Parkinson's disease, and (3) dementia. The main study outcome measures were self-reported decisions regarding diagnostic test ordering and treatment, which were assessed after each scenario. Neurologists' practice characteristics, certainty about the diagnosis, and attitudes toward uncertainty were also measured. Survey response rates were 92% of US and 63% of UK neurologists. RESULTS: A higher proportion of US than UK neurologists indicated they would order additional diagnostic tests for all three scenarios (all p < 0.05); 77% of UK compared with 26% of US neurologists would manage a single unprovoked seizure without antiepileptic medication (p < 0.0001), but treatment of early Parkinson's disease was not different. Nearly all US and UK neurologists would obtain a neuroimaging study in the evaluation of dementia. International differences persisted after adjustment for differences in demographic and practice characteristics and for attitudes toward test use and clinical uncertainty. CONCLUSIONS: We identified large international variation in clinical decisions across three common neurologic conditions. Cross-country collaboration should explore these differences to develop consensus on standards of care.

Attitude of Health Personnel↗
PubMed1998

The influence of bone and blood lead on plasma lead levels in environmentally exposed adults.

There is concern that previously accumulated bone lead stores may constitute an internal source of exposure, particularly during periods of increased bone mineral loss (e.g., pregnancy, lactation, and menopause). Furthermore, the contribution of lead mobilized from bone to plasma may not be adequately reflected by whole-blood lead levels. This possibility is especially alarming because plasma is the main circulatory compartment of lead that is available to cross cell membranes and deposit in soft tissues. We studied 26 residents of Mexico City who had no history of occupational lead exposure. Two samples of venous blood were collected from each individual. One sample was analyzed by inductively coupled plasma-magnetic sector mass spectrometry for whole-blood lead levels. The other sample was centrifuged to separate plasma, which was then isolated and analyzed for lead content by the same analytical technique. Bone lead levels in the tibia and patella were determined with a spot-source 109Cd K-X-ray fluorescence instrument. Mean lead concentrations were 0.54 microg/l in plasma, 119 microg/l in whole blood, and 23.27 and 11.71 microg/g bone mineral in the patella and tibia, respectively. The plasma-to-whole-blood lead concentration ratios ranged from 0.27% to 0.70%. Whole-blood lead level was highly correlated with plasma lead level and accounted for 95% of the variability of plasma lead concentrations. Patella and tibia lead levels were also highly correlated with plasma lead levels. The bivariate regression coefficients of patella and tibia on plasma lead were 0.034 (p<0. 001) and 0.053 (p<0.001), respectively. In a multivariate regression model of plasma lead levels that included whole-blood lead, patella lead level remained an independent predictor of plasma lead level (ss = 0.007, p<0.001). Our data suggest that although whole-blood lead levels are highly correlated with plasma lead levels, lead levels in bone (particularly trabecular bone) exert an additional independent influence on plasma lead levels. It will be important to determine whether the degree of this influence increases during times of heightened bone turnover (e.g., pregnancy and lactation).

Adult↗
PubMed1998

Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms.

The skeleton contains the majority of the body's lead burden in both children and adults. The half-life of lead in bone is in the range of years to decades, depending on bone type, metabolic state, and subject age, among other things. Measurement of skeletal lead has benefited greatly from the recent development of X-ray fluorescence (XRF) instruments that can make rapid, safe, accurate, and relatively precise measurements of lead in bone. Two types of XRF technologies exist, LXRF and KXRF; this paper focuses on KXRF, which has been the most widely validated and used. KXRF is proving to be a powerful analytical methodology for evaluating bone lead levels as a measure of time-integrated (i.e., cumulative) lead dose in epidemiologic studies of the effects of chronic lead exposure. However, insufficient attention has been given to conceptualizing the paradigms by which bone lead levels reflect lead exposure and by which the skeleton serves as an endogenous source of lead. Consideration of these paradigms, which rely on bone lead kinetics, is necessary for the proper development of a priori hypotheses involving bone lead accumulation and release, the selection of bone sites for measurement by KXRF, and the design of epidemiologic studies involving bone lead dynamics. We discuss and present supporting evidence for a conceptual model that distinguishes two major paradigms of skeletal lead, including 1) bone lead as an indicator of cumulative lead exposure (bone lead as repository), and 2) bone lead as a source of body lead burden that is mobilizable into the circulation (bone lead as source). These two roles are not mutually exclusive. Instead, they are components of the processes controlling lead accumulation into and release from bone over time. Developing successful strategies for distinguishing these two processes in epidemiologic studies will require separate measurements of lead in cortical and trabecular bone and additional measurement of specific markers of bone mineral turnover and resorption. It may also involve developing accurate methods for evaluating lead in labile compartments of the circulation, such as plasma, as a potentially useful and responsive measure of bone lead release, of the partitioning of circulatory lead, and of the toxicological significance of lead released from bone to other target organs.

Animals↗
PubMed1998

Exogenous retinoic acid during gastrulation induces cartilaginous and other craniofacial defects in Fundulus heteroclitus.

Embryonic levels of retinoic acid (RA) and the response of cells to RA are critical to the normal development of vertebrates. To understand the effects of RA signaling in Fundulus heteroclitus, we exposed embryos to a range of RA concentrations of 2 h during gastrulation. Embryos exposed to low concentrations of RA (10(-10)-10(-7) M) develop normally, whereas those exposed to higher concentrations (5 x 10(-7)-10(-4) M) develop characteristic dose-dependent defects. We describe, in detail, four stages of development that represent morphological effects of RA on (1) cell death and defects in the brain, heart, and eye, (2) relative size and differentiation, (3) duplications of pectoral fins, and (4) deletions in craniofacial cartilage elements. Analysis of cartilaginous skeletal elements demonstrates distinct patterns of deletions in the neurocranium and pharyngeal skeleton in response to increasing concentrations of RA. In F. heteroclitus, RA treatment during gastrulation results in five highly consistent phenotypes, which we have incorporated into an index of embryonic RA defects. This index should be valuable in the genetic analysis of RA pathways and in evaluating chemicals that interfere with embryonic RA signaling.

Animals↗
PubMed1998

Moderating effects of affective disposition and social support on the relationship between person-environment fit and strain.

The moderating effects of affective disposition and social support on the relationship between fit and strains were examined. Person-environment fit was measured in terms of occupational needs and reinforcers. Both positive and negative affectivity were investigated. Data were collected by means of a self-report questionnaire from 241 nurses in a Canadian hospital. Consistent with previous findings, fit was related to work satisfaction and all but one measure of psychological strain. Some support was found for the moderating effects of positive affectivity on work satisfaction and burnout, and scores on both positive and negative affectivity showed significant main effects on strain measures. Although there was no evidence of a buffering effect for social support, main effects of social support were significant for work satisfaction and one component of burnout, i.e., emotional exhaustion. Implications are discussed and recommendations for future research proposed.

Affect↗