Biomedical subjects

Donald Smith

Publications and source records attributed to Donald Smith.

At least 19 recordsLinked to original sources

PubMed2006

Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders.

BACKGROUND: Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore-processing and ferroalloy production, the risks among welders with lower exposures are less well understood. METHODS: Confined space welding in construction of a new span of the San Francisco-Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose-effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (n = 43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn-air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education. RESULTS: The mean time weighted average of Mn-air ranged from 0.11-0.46 mg/m(3) (55% >0.20 mg/m(3)). MnB >10 microg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV(1)/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose-effect relationships with CEI and/or MnB were found for IQ (p<or=0.05), executive function (p<or=0.03), sustaining concentration and sequencing (p<or=0.04), verbal learning (p<or=0.01), working (p<or=0.04) and immediate memory (p<or=0.02), even when adjusted for demographics and years of welding before Bay Bridge. Symptoms reported by the welders while working were: tremors (41.9%); numbness (60.5%); excessive fatigue (65.1%); sleep disturbance (79.1%); sexual dysfunction (58.1%); toxic hallucinations (18.6%); depression (53.5%); and anxiety (39.5%). Dose-effect associations between CEI and sexual function (p<0.05), fatigue (p<0.05), depression (p<0.01) and headache (p<0.05) were statistically significant. CONCLUSIONS: Confined space welding was shown to be associated with neurological, neuropsychological and pulmonary adverse health effects. A careful enquiry of occupational histories is recommended for all welders presenting with neurological or pulmonary complaints, and a more stringent prevention strategy should be considered for Mn exposure due to inhalation of welding fume.

Adult↗

PubMed2006

Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet.

BACKGROUND: An adverse hematological interaction between vitamins E and K has been reported, primarily in patients on anticoagulants. However, little is known regarding circulating levels or tissue concentrations of vitamin K in response to vitamin E supplementation. The purpose of this study was to examine the effect of different levels of dietary alpha-tocopherol on phylloquinone and menaquinone-4 concentrations, while maintaining a constant intake of phylloquinone, in rat tissues. METHODS: Male 4-wk old Fischer 344 rats (n = 33) were fed one of 3 diets for 12 wk: control (n = 13) with 30 mg all-rac-alpha-tocopherol acetate/kg diet; vitamin E-supplemented (n = 10) with 100 mg all-rac-alpha-tocopherol acetate/kg diet; and vitamin E-restricted (n = 10) with <10 mg total tocopherols/kg diet. All 3 diets contained 470 +/- 80 microg phylloquinone/kg diet. RESULTS: Phylloquinone concentrations were lower (P < or = 0.05) in the vitamin E-supplemented compared to the vitamin E-restricted group (mean +/- SD spleen: 531 +/- 58 vs. 735 +/- 77; kidney: 20 +/- 17 vs. 94 +/- 31, brain: 53 +/- 19 vs. 136 +/- 97 pmol/g protein respectively); no statistically significant differences between groups were found in plasma, liver or testis. Similar results were noted with menaquinone-4 concentrations in response to vitamin E supplementation. CONCLUSION: There appears to be a tissue-specific interaction between vitamins E and K when vitamin E is supplemented in rat diets. Future research is required to elucidate the mechanism for this nutrient-nutrient interaction.

Journal Article↗

PubMed2006

Biological markers of fetal lead exposure at each stage of pregnancy.

It has been suggested that plasma lead (Pb) represents the fraction of circulating Pb that crosses the placenta. Whole-blood Pb levels, the conventional method for measuring circulating Pb, may not adequately reflect plasma Pb levels. The objective of this study was to assess the relationship between whole-blood and plasma Pb in a cohort of pregnant women. A group of 237 pregnant women, recruited in Mexico City from 1997 to 1999, was studied. whole-blood and plasma lead concentrations were evaluated at 12, 24, and 34 wk of gestation by inductively coupled plasma-mass spectrometry. Data were analyzed using a mixed-effects regression model. An exponential relationship was found between plasma and whole-blood Pb levels and significant modification of the association by stage of pregnancy. The association was stronger in the second trimester relative to the first, and it further increased in the third trimester. The model predicts increased plasma Pb levels for a given whole-blood Pb value as pregnancy advances for whole-blood Pb levels greater than approximately 110 microg/L, but not for blood Pb levels less than 100 microg/L. These findings could be due to physiologic changes during pregnancy, such as decreasing hematocrit, saturation of red cell Pb binding capacity, and increased bone resorption or intestinal absorption. Collectively, these data suggest that at elevated maternal blood Pb levels the developing fetus may be at greater risk of Pb exposure from increased maternal plasma Pb than otherwise predicted from whole-blood Pb levels.

Adult↗

PubMed2006

Augmentation of anterior lumbar interbody fusion with anterior pedicle screw fixation: demonstration of novel constructs and evaluation of biomechanical stability in cadaveric specimens.

OBJECTIVE: Anterior lumbar interbody fusion (ALIF) has proven effective for indications including discogenic back pain, nonunion, and instability. Current practice involves posterior pedicle screw augmentation of the ALIF procedure (ALIF-PPS). This approach requires intraoperative repositioning of the patient for percutaneous posterior pedicle screw placement. We have developed a novel technique in which the ALIF procedure is augmented with anterior pedicle screws (APS; ALIF-APS). In this study, we introduce this new technique and compare the biomechanical stability of the novel ALIF-APS with the current standard ALIF-PPS. METHODS: The technique was demonstrated in a cadaveric L4-S1 specimen using neuronavigation and fluoroscopy. Plain radiographs and computed tomographic scans of the construct were obtained. Twelve cadaveric spines (7 men and 5 women) from donors with an average age of 81 years (range, 64-93 yr) were then harvested from L4-S1. Six specimens were dedicated to ALIF-APS constructs, and the remaining six were dedicated to ALIF-PPS constructs. The specimens were then studied at L5-S1 in the following steps: 1) intact form, 2) after anterior discectomy, 3) after implantation of titanium cages (ALIF), and 4) after APS or PPS fixation in conjunction with the ALIF. Measurements were obtained in axial rotation and left and right lateral bending flexion-extension. Data were normalized by calculating the ratio of the stiffness of the instrumented to the intact spine. Statistical analyses were then performed on the data. RESULTS: Radiographs and computed tomographic scans of the construct showed accurate placement of the APS at L5 and S1. The normalized data showed that ALIF-APS and ALIF-PPS had approximately equal stability in axial rotation (1.17 +/- 0.43 versus 0.85 +/- 0.14), lateral bending (0.93 +/- 0.22 versus 0.95 +/- 0.16), and flexion- extension (0.77 +/- 0.13 versus 0.84 +/- 0.2). Paired t test analysis did not show a significant difference between the biomechanical stiffness of ALIF-APS and ALIF-PPS in axial rotation, lateral bending, and flexion-extension. CONCLUSION: We demonstrate a new technique in a cadaveric specimen whereby the ALIF procedure is augmented with APS fixation using neuronavigation and fluoroscopy. Biomechanical evaluation of the constructs suggests that the ALIF-APS has comparable stability with ALIF-PPS. APS augmentation of ALIF has potential advantages over the current standard ALIF-PPS because it can 1) eliminate the patient repositioning step, 2) minimize the total number of incisions and the total operative time, and 3) protect against dislocation of the ALIF interbody graft or cage. Work is in progress to develop a low-profile system for the novel APS constructs described here.

Aged↗

PubMed2006

Accuracy of pedicle screw placement for lumbar fusion using anatomic landmarks versus open laminectomy: a comparison of two surgical techniques in cadaveric specimens.

OBJECTIVE: We determined whether the accuracy of lumbar pedicle screw placement is optimized by performing a laminectomy before screw placement with screw entry point and trajectory being guided by pedicle visualization and palpation (Technique 1). This technique was compared with a technique using anatomic landmarks for pedicle screw placement (Technique 2). The biomechanical stability of the instrumented constructs, in the absence and presence of a laminectomy, was also compared. METHODS: Twelve L1-L3 specimens were harvested from fresh cadavers. The intact laminectomy and instrumented spines were biomechanically tested in flexion and extension, lateral bending, and axial rotation. Laminectomies were performed in six of the 12 specimens before pedicle screw placement using Technique 1. The remaining six specimens underwent pedicle screw and rod fixation using Technique 2. Computed tomographic images were obtained for all instrumented specimens. Deviation of the screws from the ideal entry point or trajectory was analyzed to quantitatively compare the two techniques. RESULTS: Computed tomographic analysis of the specimens showed that all screw placements were within the pedicles. Scatter plot analysis demonstrated that screws placed using Technique 2 were more likely to have the combination of entry points and trajectories medial to the ideal entry point and trajectory. Laminectomy did not weaken the final pedicle screw and rod-fixated constructs. CONCLUSION: All screw placements were grossly within the confines of the pedicles, regardless of technique, as evidenced by computed tomographic analysis. Furthermore, the anatomic landmark technique and the open laminectomy technique yielded biomechanically equivalent pedicle screw and rod-fixated constructs.

Aged↗

PubMed2006

Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development.

BACKGROUND: The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure. OBJECTIVE: We studied prenatal lead exposure's impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels. METHODS: We measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose. RESULTS: Maternal lead levels were moderately high with a first-trimester blood lead mean (+/- SD) value of 7.1 +/- 5.1 microg/dL and 14% of values >or=10 microg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors (p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores. CONCLUSIONS: Fetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood.

Adolescent↗

PubMed2006

Predictive factors for dural tear and cerebrospinal fluid leakage in patients undergoing lumbar surgery.

OBJECT: A dural tear resulting in a cerebrospinal fluid (CSF) leak is a well-known risk of lumbar spinal procedures. The authors hypothesized that the incidence of CSF leakage is higher in cases involving repeated operations and those in which the surgeon performing the surgery is less experienced; however, they postulated that the overall outcome of the patient would not be adversely affected by a dural tear. METHODS: An institutional review board-approved protocol at Louisiana State University Health Sciences Center, Shreveport, was initiated in August 2003 to allow prospective comparison of data obtained in patients in whom a CSF leak occurred (Group A) and those in whom no CSF leak occurred (Group B) during lumbar surgery. Basic demographic information, descriptive findings regarding the tear, history of other surgeries, hospital length of stay (LOS), and immediate disposition at the time of discharge were compared between the two groups. Seventy-seven patients were eligible for this study. One patient refused to participate. In 12 (15.8%) of 76 patients CSF leakage developed. In three patients the presence of a tear was questioned, and the patients were clinically treated as if a tear were present. The patients in Group A were older than those in Group B (59.8 +/- 16.9 and 49.4 +/- 13.6 years of age, respectively; p = 0.02, Fisher exact test). In terms of those with a history of surgery, there was no significant difference between patients with and patients without a CSF leak (three [25%] of 12 patients [Group A] compared with 28 [43.8%] of 64 patients [Group B]; p = 0.34, two-sample t-test). In the 12 patients with dural tears, nine (75%) were caused by a resident-in-training, and the Kerrison punch was the instrument most often being used at the time (55%). This is significantly greater than 50% at the 5% level (p = 0.044, binomial test). The authors were able to repair the tear primarily with suture in all but one patient, whose tear was along the nerve root sleeve. In all cases fibrin glue and a muscle/fat graft were used to cover the tear, and all patients were assigned to bed rest from 24 to 48 hours after the operation. In Group A one patient required rehabilitation at discharge. The LOS in Group A was greater than that in Group B (median 5 days compared with 3 days), but no additional complication was noted. CONCLUSIONS: The incidence of CSF leakage was 16% in 76 patients, and there were no other complications. Older patient age and higher level of the surgeon's training were factors contributing to the incidence, but the history of surgery was not.

Adult↗

PubMed2005

Issues in neurological risk assessment for occupational exposures: the Bay Bridge welders.

The goal of occupational risk assessment is often to estimate excess lifetime risk for some disabling or fatal health outcome in relation to a fixed workplace exposure lasting a working lifetime. For sub-chronic or sub-clinical health effects measured as continuous variables, the benchmark dose method can be applied, but poses issues in defining impairment and in specifying acceptable levels of excess risk. Such risks may also exhibit a dose-rate effect and partial reversibility such that effects depend on how the dose is distributed over time. Neurological deficits as measured by a variety of increasingly sensitive neurobehavioral tests represent one such outcome, and the development of a parkinsonian syndrome among welders exposed to manganese fume presents a specific instance. Welders employed in the construction of piers for a new San Francisco-Oakland Bay Bridge in San Francisco were previously evaluated using a broad spectrum of tests. Results for four of those tests (Rey-Osterrieth Complex Figure Test, Working Memory Index, Stroop Color Word Test and Auditory Consonant Trigrams Test) were used in the benchmark dose procedure. Across the four outcomes analyzed, benchmark dose estimates were generally within a factor of 2.0, and decreased as the percentile of normal performance defining impairment increased. Estimated excess prevalence of impairment, defined as performance below the 5th percentile of normal, after 2 years of exposure at the current California standard (0.2 mg/m3, 8 h TWA), ranged 15-32% for the outcomes studied. Because these exposures occurred over a 1-2-year period, generalization to lifetime excess risk requires further consideration of the form of the exposure response and whether short-term responses can be generalized to equivalent 45-year period. These results indicate unacceptable risks at the current OSHA PEL for manganese (5.0 mg/m3, 15 min) and likely at the Cal OSHA PEL as well.

Adult↗

PubMed2005

Assessment of pain control, quality of life, and predictors of success after gamma knife surgery for the treatment of trigeminal neuralgia.

OBJECT: There are various surgical treatment alternatives for trigeminal neuralgia (TN), but there is no single scale that can be used uniformly to assess and compare one type of intervention with the others. In this study the objectives were to determine factors associated with pain control, pain-free survival, residual pain, and recurrence after gamma knife surgery (GKS) treatment for TN, and to correlate the patients' self-reported quality of life (QOL) and satisfaction with the aforementioned factors. METHODS: Between the years 2000 and 2004, the authors treated 81 patients with medically refractory TN by using GKS. Fifty-two patients responded to a questionnaire regarding pain control, activities of daily living, QOL, and patient satisfaction. The median follow-up duration was 16.5 months. Twenty-two patients (42.3%) had complete pain relief, 14 (26.9%) had partial but satisfactory pain relief, and in 16 patients (30.8%) the treatment failed. Seven patients (13.5%) reported a recurrence during the follow-up period, and 25 (48.1%) reported a significant (> 50%) decrease in their pain within the 1st month posttreatment. The mean decrease in the total dose of pain medication was 75%. Patients' self-reported QOL scores improved 90% and the overall patient satisfaction score was 80%. CONCLUSIONS: The authors found that GKS is a minimally invasive and effective procedure that yields a favorable outcome for patients with recurrent or refractory TN. It may also be offered as a first-line surgical modality for any patients with TN who are unsuited or unwilling to undergo microvascular decompression.

Adult↗

PubMed2005

Role of stereotactic radiosurgery as a primary treatment option in the management of newly diagnosed multiple (3-6) intracranial metastases.

OBJECTIVE: The objective of this study was to assess the role of stereotactic radiosurgery in the management of newly diagnosed multiple intracranial metastases from known primary cancer locations. METHODS: Fifty (29 women and 21 men) patients received radiosurgery for newly diagnosed 3 or more metastatic brain tumors. Their mean age was 53 years. Lung cancer was the most common primary cancer (66%). RESULTS: Arrest in the growth of irradiated tumors was achieved in 41 (82%) patients. Eight patients (16%) required further intervention for tumors in other brain locations. Mean survival after diagnosis of brain disease was 12 months and the brain disease-controlled period was 19 months. The period of brain disease control prolonged (P=.03) with decreasing tumor volumes (<10 mL). Control of treated tumors positively affected survival after diagnosis of brain disease (P=.0001). CONCLUSION: Radiosurgery as an adjuvant improves survival in patients with cancer who have newly diagnosed multiple intracranial metastases by arresting the growth of tumors.

Adult↗

PubMed2005

A noninvasive isotopic approach to estimate the bone lead contribution to blood in children: implications for assessing the efficacy of lead abatement.

Lead hazard control measures to reduce children's exposure to household lead sources often result in only limited reductions in blood lead levels. This may be due to incomplete remediation of lead sources and/or to the remobilization of lead stores from bone, which may act as an endogenous lead source that buffers reductions in blood lead levels. Here we present a noninvasive isotopic approach to estimate the magnitude of the bone lead contribution to blood in children following household lead remediation. In this approach, lead isotopic ratios of a child's blood and 5-day fecal samples are determined before and after a household intervention aimed at reducing the child's lead intake. The bone lead contribution to blood is estimated from a system of mass balance equations of lead concentrations and isotopic compositions in blood at the different times of sample collection. The utility of this method is illustrated with three cases of children with blood lead levels in the range of 18-29 microg/dL. In all three cases, the release of lead from bone supported a substantial fraction of the measured blood lead level postintervention, up to 96% in one case. In general, the lead isotopic compositions of feces matched or were within the range of the lead isotopic compositions of the household dusts with lead loadings exceeding U.S. Environmental Protection Agency action levels. This isotopic agreement underscores the utility of lead isotopic measurements of feces to identify household sources of lead exposure. Results from this limited number of cases support the hypothesis that the release of bone lead into blood may substantially buffer the decrease in blood lead levels expected from the reduction in lead intake.

Bone and Bones↗

PubMed2004

Impact of bone lead and bone resorption on plasma and whole blood lead levels during pregnancy.

The authors tested the hypotheses that maternal bone lead burden is associated with increasing maternal whole blood and plasma lead levels over the course of pregnancy and that this association is modified by rates of maternal bone resorption. A total of 193 Mexican women were evaluated (1997-1999) in the first, second, and third trimesters of pregnancy. Whole blood lead and plasma lead levels were measured in each trimester. Urine was analyzed for cross-linked N-telopeptides (NTx) of type I collagen, a biomarker of bone resorption. Patella and tibia lead levels were measured at 4 weeks postpartum. The relation between whole blood, plasma, and bone lead and NTx was assessed using mixed models. Plasma lead concentrations followed a U-shape, while NTx levels increased significantly during pregnancy. In a multivariate model, the authors observed a significant and positive interaction between NTx and bone lead when plasma lead was used as the outcome variable. Dietary calcium intake was inversely associated with plasma lead. Results for whole blood lead were similar but less pronounced. These results confirm previous evidence that bone resorption increases during pregnancy, with a consequential significant release of lead from bone, constituting an endogenous source of prenatal exposure. They also provide a rationale for testing strategies (e.g., nutritional supplementation with calcium) aimed at decreasing prenatal lead exposure.

Adolescent↗

PubMed2004

Vitamin E supplementation suppresses macrophage accumulation and endothelial cell expression of adhesion molecules in the aorta of hypercholesterolemic rabbits.

Suppression of cell adhesion molecule expression and macrophage accumulation by the endothelium is believed to play an important role in preventing the development of atherosclerosis. Earlier, we have shown that in vitro supplementation of human aortic endothelial cells with Vitamin E dose-dependently reduced expression of adhesion molecules and monocyte adhesion. Here, we report the in vivo down-regulation of endothelial cell adhesion molecules expression and macrophage accumulation in the aortas of hypercholesterolemic rabbits supplemented with Vitamin E. To this end, New Zealand White rabbits were fed a semi-purified diet containing 30 (control) or 1000 IU/kg Vitamin E. After 4 weeks, both groups' diets were switched to an atherogenic diet (0.3% cholesterol, 9% hydrogenated coconut oil, and 1% corn oil) containing the respective levels of Vitamin E and fed for 2, 4, and 6 weeks. Vitamin E supplemented rabbits had significantly higher levels of Vitamin E in their plasma and aortas. Frozen aorta sections were fixed and stained by an avidin-biotin complex method using Rb2/3 and Rb1/9 monoclonal antibodies against rabbit ICAM-1 and VCAM-1, respectively, and with RAM-11 for macrophage and von Willebrand factor for endothelial cells, followed by staining with secondary antibodies and counterstaining and evaluation under the microscope. At 6 weeks on atherogenic diet treatment, a trend (P = 0.08) toward a lower score of ICAM-1 expression by endothelial cells was observed in the aorta of Vitamin E treated rabbits compared to the control. However, a decrease in the score of VCAM-1 expression by endothelial cells in Vitamin E treated rabbits did not reach to a statistical significance. At 4 and 6 weeks on atherogenic diet, Vitamin E supplementation also significantly (P = 0.003) inhibited the accumulation of macrophages in the aorta. These results support the concept that down-regulation of adhesion molecule expression and suppression of monocyte/macrophage activation by Vitamin E in vivo is one of the potential mechanisms by which Vitamin E may suppress the development of aortic lesions in a rabbit model of atherosclerosis.

Administration, Oral↗

PubMed2004

Survival trends in elderly patients with glioblastoma multiforme: resective surgery, radiation, and chemotherapy.

BACKGROUND: It is appropriate to investigate and to determine survival trends following glioblastoma multiforme treatment using resective surgery, radiation therapy, and/or chemotherapy in patients aged 59 years and higher. METHODS: We retrospectively reviewed 30 elderly patients (> or =59 years old) who were treated for histopathologically confirmed glioblastoma multiforme at our tertiary care institution from 1990 through 2002. All patients were treated with steroids. In addition, 22 patients underwent resective surgery (RS), 17 patients underwent radiation therapy (RT), and 10 patients underwent chemotherapy (C). Many patients underwent these treatments in various combinations: 6 underwent biopsy only, 7 RS only, 6 RS+RT only, and 9 RS+RT+C. For each case, pre-treatment Karnofsky performance scores (KPS), tumor location, presenting symptoms and signs, associated surgical morbidity, and pre-existing medical conditions were also recorded. Patients were categorized into one of four treatment subgroups: Biopsy only, RS only, RS+RT, and RT+RS+C. For each of these subgroups, pretreatment KPS and post-treatment survival were compared. RESULTS: Post-treatment survival following biopsy only was 3.2 +/- 0.8 months (mean +/- SE); RS 2.2 +/- 0.5; RS+RT 5.5 +/- 1.2; RS+RT+C 13.6 +/- 2.1. A longer survival trend was noted for the RS+RT versus RS group (two-tailed unpaired t test, p = 0.02;), as well as the RS+RT+C group, which showed consistently higher survival in comparison to most of the other groups (p = 0.0021, 0.00039, 0.013 vs. the biopsy only, RS only, and RS+RT groups, respectively). No significant difference was found in KPS, comparing all individual groups versus each other (p > or = 0.06). Remarkably, 6 patients survived over 14 months (range, 14.1-22.7 months), all of which received RS+RT+C. CONCLUSIONS: This study suggests a significant improvement in elderly patients treated with the combination of resective surgery, radiation therapy, and chemotherapy, rather than either treatment alone or other combination. This significant improvement does not appear to be biased by pretreatment KPS, as mean KPS values did not significantly differ between any of these groups. However, a greater number of patients in each group must be considered to achieve the power to make more definitive treatment guidelines.

Age Factors↗

PubMed2004

Reductions in blood lead overestimate reductions in brain lead following repeated succimer regimens in a rodent model of childhood lead exposure.

Although many studies have demonstrated the efficacy of succimer chelation in reducing blood and brain lead levels, the relative efficacy of the drug in the two tissues is less well understood. This issue is important because blood lead levels after chelation are used clinically to estimate reductions in the brain, the most critical organ in considering lead-induced neurotoxicity. The present study was designed to further investigate this issue, using multiple chelation regimens. Long-Evans rats were exposed to one of three lead exposure regimens from birth until postnatal day 40, followed by treatment with succimer (one or two 3-week regimens) or vehicle. The results indicated that one succimer regimen was significantly superior to vehicle treatment in lowering lead levels in both blood and brain across the entire 8-week follow-up period. Similarly, a second succimer regimen offered significant additional benefit relative to one regimen for both blood and brain across the 4-week follow-up period. However, several findings revealed that succimer-induced reductions in brain lead lagged behind reductions in blood lead and were generally smaller in magnitude. Furthermore, a rebound was detected in blood, but not brain, lead levels after both succimer regimens. Given the results of this study, we urge caution in using blood lead as a surrogate for brain lead levels, particularly during and immediately after chelation treatment when reductions in blood lead levels overestimate reductions in brain lead levels. The present results suggest that, in clinical use, succimer treatment may need to extend beyond the point at which blood lead levels have dropped to an "acceptable" target value in order to effectively reduce brain lead levels and minimize neurotoxicity.

Animals↗

PubMed2003

Alterations in cellular IRP-dependent iron regulation by in vitro manganese exposure in undifferentiated PC12 cells.

Manganese (Mn) may interfere with iron regulation by altering the binding of iron regulatory proteins (IRPs) to their response elements found on the mRNA encoding proteins critical to iron homeostasis. To explore this, the effects of 24-h in vitro manganese exposure (1, 10, 50, and 200 microM Mn) on: (i) total intracellular and labile iron concentrations; (ii) the cellular abundance of transferrin receptor (TfR), H- and L-ferritin, and mitochondrial aconitase proteins; and (iii) IRP binding to a [32P](-) labeled mRNA sequence of L-ferritin were evaluated in undifferentiated PC12 cells. In vitro manganese exposure altered the cellular abundance of TfR, H-/L-ferritin, and m-aconitase, resulting in an increase in labile iron. This latter effect led to a decrease in IRP binding activity at the lower (10 and 50 microM) manganese exposures. In contrast, 200 microM manganese exposure increased IRP binding, in spite of the significant increase in labile iron. These data indicate that at lower exposures, manganese directly interfered with IRP-dependent translational events, producing an increase in labile iron, which in turn signaled a decrease in IRP binding at 24 h. At higher exposures, the intracellular burden of manganese resulted in overt cytotoxicity and appeared to compromise the normal compensatory response to increased labile iron, producing increased IRP binding. We conclude that low to moderate manganese exposure interferes with cellular iron regulation, and thus may serve as a contributory mechanism underlying manganese neurotoxicity.

Animals↗

PubMed2003

The prevalence of female-to-male intimate partner violence in an urban emergency department.

Female-to-male intimate partner violence (IPV) recently has become a recognized health care issue. We screened a heterosexual male Emergency Department population for IPV using the HITS scale, a four-question survey. Two hundred eighty-two men were enrolled in the study. Basic demographics, along with the answers to the HITS scale, were analyzed. Of the men screened, 29.3% had a positive history of IPV. Men who were positive for IPV were more likely to score higher on questions regarding the frequency of verbal aggression than actual or threatened physical violence. This study reinforces the need to screen both genders for IPV in the Emergency Department.

Adult↗

PubMed2003

Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain.

Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [(11)C]raclopride to dopamine D(2,3) receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [(11)C]raclopride for dopamine D(2,3) receptors. However, the sensitivity of [(11)C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [(11)C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [(15)O]water. Neither a low dose of nicotine (50 mu kg(-1), iv) nor a high dose of nicotine (500 microg kg(-1), iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [(11)C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [(11)C]raclopride by 10% in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition between endogenous dopamine for [(11)C]raclopride binding sites with a complex temporal and spacial pattern in pig brain, initially presenting in the left ventral striatum.

Animals↗