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1.
Neurophysiol Clin ; 44(2): 227-33, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24930945

ABSTRACT

AIM: Although gait initiation has been extensively studied, gait termination has received less attention. In particular, the trajectory of the centre of pressure (CoP) during gait termination, as well as the trajectory's determinants, has not yet been described. The purpose of the present study was to characterize the kinetic components of planned gait termination (including the CoP trajectory) with respect to the various gait events and centre of mass speed and trajectory. METHODS: Thirty healthy subjects were asked to walk along a test track and stop on a force platform while an optoelectronic system recorded temporal and spatial parameters. A total of 90 trials were analysed. RESULTS: Subjects needed two steps to stop on the force platform. The CoP trajectory during gait termination was composed of three phases. During the first phase, the CoP moved forward under the stance foot, which was in contact with the ground. The ground reaction forces exerted a sagittal braking action. The second phase showed a lateral CoP shift and was correlated with braking; this may correspond to anticipatory postural adjustments for gait termination. The third and last phase might correspond to compensatory adjustments before the stance phase. CONCLUSIONS: CoP trajectory is more complex during gait termination than during gait initiation. Gait termination comprises several specific sequences in the gait-stance transition. A better understanding of the kinetic parameters in gait termination should enable us to identify which kinetic parameters could be considered as risk factors for falls.


Subject(s)
Gait , Adult , Biomechanical Phenomena , Female , Humans , Male , Middle Aged , Pressure
2.
Clin Neurophysiol ; 122(10): 2032-5, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21507712

ABSTRACT

OBJECTIVE: Although it is well known that postural adjustment (PA) is impaired in advanced Parkinson's disease (PD), the potentially compensatory effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in this respect are less clear. METHODS: While standing on a force platform and in the absence of antiparkinsonian medication, 10 patients performed voluntary, unilateral arm movements before surgery (the 'off stim' condition) and then afterwards (the 'on stim' condition). The patients' PAs were monitored by vertical torque (Tz) and compared with those recorded in control subjects. RESULTS: Patients with STN DBS and control subjects showed similar values for PA amplitude, duration and latency. CONCLUSIONS: STN stimulation may induce better postural control during the movement preparation and execution phases. Our results argue in favour of a positive effect of STN DBS on PA. SIGNIFICANCE: The PA amplitude (provided by Tz) may be a strong marker reflecting the clinical improvement seen in stimulated PD patients.


Subject(s)
Arm/physiology , Deep Brain Stimulation/methods , Movement/physiology , Parkinson Disease/physiopathology , Posture/physiology , Subthalamic Nucleus/physiology , Aged , Female , Humans , Male , Middle Aged , Parkinson Disease/therapy
3.
J Neural Transm (Vienna) ; 115(10): 1431-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18726136

ABSTRACT

Freezing of gait (FOG) in Parkinson's disease (PD) is defined as a sudden inability to maintain effective stepping movements. However, its pathophysiology remains unclear. The objectives are: (1) To assess the contribution of both spatial (walking speed, stride length) and temporal parameters (cadence, stride time) and their coefficients of variation to the genesis of FOG in PD. (2) To evaluate whether and how externally imposed modifications of self-determined gait would elicit FOG. We included ten patients with advanced PD, and with daily off drug FOG episodes. We focused on walking in an open runway. For each subject, we manipulated gait by externally imposing four changes in walking speed and four changes in cadence. FOG episodes, often with a long duration of more than 5-s, were observed mostly under conditions with a high imposed cadence. The steps that immediately preceded these episodes were mainly characterized by an increase in cadence and an increase in stride length variability. The results also underscore that FOG can be elicited in a laboratory setting when patients are placed under considerable strain, at least in advanced stages of PD. Patients were unable to adequately negotiate the extreme imposed cadence condition, and this resulted in frequent FOG episodes, even while walking in an open runway. Placing advanced PD patients into extreme imposed conditions leads to a motor wise and mental collapse response, culminating in FOG. Future work should establish the relevance of these findings for the more common forms of FOG, including brief episodes during turning or gait initiation.


Subject(s)
Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Gait/physiology , Parkinson Disease/physiopathology , Stress, Psychological/complications , Aged , Humans , Parkinson Disease/complications , Parkinson Disease/psychology , Walking/physiology , Walking/psychology
4.
Neurology ; 71(2): 80-4, 2008 Jul 08.
Article in English | MEDLINE | ID: mdl-18420482

ABSTRACT

BACKGROUND: Severe gait disturbances and freezing episodes (frequently resistant to optimal dopaminergic treatment) often appear in advanced Parkinson disease (PD). Even several years after initiation, high-frequency subthalamic nucleus deep brain stimulation (STN-DBS) is still very effective for controlling segmental symptoms. However, there are no long-term data on the management of gait disorders and freezing in STN-DBS. OBJECTIVES: To compare the effects of various STN-DBS parameters on freezing of gait and to determine whether such effects are more related to stimulation energy (usual voltages vs high voltages at 130 Hz) or frequency (130 Hz vs approximately half this frequency: 60 Hz). METHODS: We blindly assessed STN-DBS parameters in 13 PD patients reporting severe gait disorders. We compared the effects on gait of two different voltages (the patient's usual voltage [median 3 volts] and a high voltage [median 3.7 volts]) and two different frequencies (60 and 130 Hz, while maintaining the same total energy delivered) vs "off-stimulation" conditions. RESULTS: The number of freezing episodes was significantly lower at the 60-Hz "high voltage/equivalent energy" and higher at the 130-Hz/high voltage than for "off stimulation." The slight improvement in the Unified Parkinson's Disease Rating Scale motor score observed (at 130 Hz) did not achieve statistical significance. CONCLUSIONS: Our results prompt consideration of a new strategy for two-stage subthalamic nucleus deep brain stimulation (STN-DBS) frequency optimization, with stimulation at 130 Hz and the usual voltage during the initial years of STN-DBS and then at 60 Hz at a high voltage in Parkinson disease patients who develop severe gait disorders.


Subject(s)
Deep Brain Stimulation/methods , Gait , Muscle Rigidity/etiology , Muscle Rigidity/prevention & control , Parkinson Disease/complications , Parkinson Disease/therapy , Accidental Falls/prevention & control , Cognition Disorders/etiology , Deep Brain Stimulation/adverse effects , Follow-Up Studies , Humans , Pedunculopontine Tegmental Nucleus/physiopathology , Pedunculopontine Tegmental Nucleus/surgery , Subthalamic Nucleus/physiopathology
5.
Neurophysiol Clin ; 38(2): 117-25, 2008 Apr.
Article in French | MEDLINE | ID: mdl-18423332

ABSTRACT

INTRODUCTION: Locomotion disorders are important in Huntington's disease (HD). Although the rates of evolution of motor, functional or cognitive aspects of HD have been studied, the evolution of locomotion disorders in early stages of the disease remains unknown. OBJECTIVES: To determine the rate of evolution of the HD-associated gait and gait initiation disorders and their correlates. PATIENTS AND METHODS: Eighteen HD patients were recorded with a minimum interevaluation interval of one year. Akinesia was studied by evaluating the anticipatory postural adjustment (APA) phase preceding the first step. We also evaluated gait speed, stride time and stride length. RESULTS: We observed an alteration in the APA phase, whose evolution was correlated with that of akinesia. We also observed a decrease in gait speed, which was due both to an increase in stride time and a decrease in stride length. Stride-to-stride variability did not worsen between both evaluations. CONCLUSIONS: A worsening in both gait initiation and gait performance was observed in HD. Initial weak functional capacity and more severe motor impairment seem to be associated with a faster progression of locomotion parameters in these mildly impaired HD patients.


Subject(s)
Huntington Disease/physiopathology , Locomotion/physiology , Aged , Biomechanical Phenomena , Disease Progression , Dyskinesias/etiology , Dyskinesias/physiopathology , Female , Humans , Huntington Disease/psychology , Male , Middle Aged , Neuropsychological Tests , Posture/physiology , Psychomotor Performance/physiology
6.
Heart ; 94(8): 1032-7, 2008 Aug.
Article in English | MEDLINE | ID: mdl-17947362

ABSTRACT

BACKGROUND: Risk stratification for patients with acute dyspnoea is a challenging task. No quantitative tool for mortality prediction among patients with acute dyspnoea is available. METHODS: 595 dyspnoeic subjects were enrolled in an emergency department. Clinical and biochemical factors independently predictive of death by 1 year were used to develop a mortality risk prediction tool. RESULTS: Seven factors comprised the final tool: age (x0.3), heart rate (x0.2), blood urea nitrogen (x0.3), New York Heart Association class (x5), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) >or=986 pg/ml (18 points), systolic blood pressure <100 mm Hg (11 points) and presence of a murmur (11 points). A continuous rise in mortality was seen from 1.7% in the lowest score quintile (n = 118; score or=85.5; p<0.001 for trend). Receiver operating characteristic curve analysis of the score's accuracy produced an area under the curve (AUC) of 0.82 (95% CI 0.78 to 0.85) with similar AUCs in subjects with acutely destabilised heart failure (AUC = 0.73, 95% CI 0.67 to 0.79) and those without (AUC = 0.83, 95% CI 0.77 to 0.85, p for the comparison = NS). The score was validated in a separate population of dyspnoeic patients (AUC = 0.73, 95% CI 0.64 to 0.82; p<0.001) and was incorporated into a computer program suitable for near-patient calculation. CONCLUSION: A new risk stratification tool for acutely dyspnoeic patients has been derived and validated.


Subject(s)
Diagnosis, Computer-Assisted/methods , Dyspnea/etiology , Acute Disease , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Emergency Service, Hospital , Epidemiologic Methods , Female , Heart Failure/complications , Heart Failure/diagnosis , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Point-of-Care Systems , Prognosis
7.
J Neurol Neurosurg Psychiatry ; 79(8): 881-7, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18039891

ABSTRACT

OBJECTIVE: To study anticipatory postural adjustments (APAs) in Parkinson's disease (PD) via a biomechanical analysis, including vertical torque (Tz). METHODS: Ten patients with PD (in the "off-drug" condition) and 10 age matched controls were included. While standing on a force platform, the subject performed a right shoulder flexion in order to grasp a handle in front of him/her, under three conditions (all at maximal velocity): movement triggered by a sound signal and loaded/non-loaded, self-paced movement. The anteroposterior coordinates of the centre of pressure (COP) and Tz were calculated. RESULTS: A group effect was observed for Tz and COP in patients with PD (compared with controls): the maximal velocity peak appeared later and the amplitude of the COP backward displacement and the area of the positive phase of Tz were lower, whereas the duration of the positive phase of Tz was greater. Interaction analysis showed that the area of Tz was especially affected in the triggered condition and the loaded, self-paced condition. The onset of the COP backward displacement was delayed in the triggered condition. CONCLUSION: Our biomechanical analysis revealed that patients with PD do indeed perform APAs prior to unilateral arm movement, although there were some abnormalities. The reduced APA magnitude appears to correspond to a strategy for not endangering postural balance.


Subject(s)
Arm/physiopathology , Kinesthesis/physiology , Parkinson Disease/physiopathology , Postural Balance/physiology , Psychomotor Performance/physiology , Weight-Bearing/physiology , Aged , Biomechanical Phenomena , Female , Hand Strength/physiology , Humans , Male , Middle Aged , Orientation/physiology , Parkinson Disease/diagnosis , Reaction Time/physiology , Torque
8.
Gait Posture ; 25(2): 279-88, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16820294

ABSTRACT

BACKGROUND: Akinesia in basal ganglia disorders is essentially defined by delayed movement initiation; the reaction time increases and it becomes difficult (or even impossible) for the subject to initiate movement. A biomechanical study of gait initiation would help evaluate the role of akinesia in early stage Huntington's disease (HD) patients. METHODS: We recorded kinematic, spatiotemporal and angular parameters (using video motion analysis, a force platform and an optoelectronic system) for the first two steps taken by 15 HD patients and 15 gender- and age-matched controls. In order to evaluate the influence of an external cue on gait initiation parameters, we studied two movement paradigms: self-triggered initiation and initiation triggered (cued) by a "beep" sound. We analyzed kinematic, spatiotemporal (the speed, length and duration of the two first steps) and angular parameters (range of joint angles) as well as kinetic data (the trajectory of the centre of pressure (COP); the speed and trajectory of the centre of mass (COM)). RESULTS: HD patients presented akinesia in both externally triggered and self-triggered conditions. Patients had more difficulties with self-triggered gait than with triggered gait. In HD, anticipatory postural adjustments (APAs) were more impaired in self-triggered gait initiation than in cued initiation. Indeed, an alteration in the kinetic parameters revealed a reduction in first step speed in both conditions. Hypokinesia (as assessed by a reduction in the range of angle joints) played an important role in this reduction. CONCLUSION: Akinesia is a major feature of impaired gait initiation in HD. The deficiencies in self-triggered initiation in HD seen here fit with a hypothesis whereby deficient internal cueing can be replaced by an external trigger.


Subject(s)
Cues , Gait Disorders, Neurologic/physiopathology , Huntington Disease/physiopathology , Biomechanical Phenomena , Case-Control Studies , Electromyography , Female , Humans , Hypokinesia/physiopathology , Joints/physiopathology , Male , Middle Aged , Muscle, Skeletal/physiopathology , Range of Motion, Articular/physiology
9.
J Neurol ; 253(5): 594-600, 2006 May.
Article in English | MEDLINE | ID: mdl-16525880

ABSTRACT

BACKGROUND: Bilateral pallidal lesions induce a range of cognitive and motor disorders, principally a parkinsonian syndrome in which severe disturbances of gait and gait initiation are frequently reported. However, the precise clinical features of these disorders (and the role of the pallidum therein) remain to be established. OBJECTIVES: The goal of this study was to characterise gait and gait initiation disorders within the context of a parkinsonian syndrome in patients with acquired, bilateral, pallidal lesions (PAL patients), to compare these disorders to those seen in Parkinson's disease (PD), and to assess the corresponding physiopathological implications. PATIENTS AND METHODS: By using a video motion analysis system (VICON), we studied gait kinematic parameters in two patients presenting with bilateral, pallidal lesions. Kinematic and kinetic parameters were also determined during gait initiation. The two patients were compared with a group of 17 PD patients and to 20 healthy controls. RESULTS: In both PAL and PD patients, kinematic parameters (gait and gait initiation) and kinetic parameters (gait initiation) were similarly impaired, evidenced by akinesia (difficulty in initiating gait characterized by impairment of anticipatory postural adjustments). Hypokinesia and bradykinesia (respectively reduced stride length and reduced speed during gait) were also noted. CONCLUSION: The gait and gait initiation disorders seen in cases of bilateral pallidal lesions (namely akinesia, hypokinesia and bradykinesia) are similar to those observed in PD. Subject to confirmation in more extensive studies, we hypothesize that bipallidal patients may present higher level gait disorders,with potential mediation by cognitive impairment.


Subject(s)
Brain Injuries/complications , Brain Injuries/pathology , Gait Disorders, Neurologic/etiology , Globus Pallidus/pathology , Aged , Biomechanical Phenomena , Gait Disorders, Neurologic/pathology , Globus Pallidus/physiopathology , Humans , Magnetic Resonance Imaging/methods , Male , Motor Activity/physiology , Neurologic Examination/methods , Parkinson Disease/physiopathology
10.
Neurophysiol Clin ; 35(5-6): 180-90, 2005.
Article in French | MEDLINE | ID: mdl-16530136

ABSTRACT

OBJECTIVE: Preparation of upper-limb movements differs between self-paced and triggered conditions. This study analyzed the anticipatory postural adjustments (APAs) of gait initiation in normal subjects in 2 conditions: self-generated and triggered by a "beep" sound. METHODS: We recorded kinematic, spatiotemporal parameters of the first two steps by means of video motion analysis (6 infrared cameras), and kinetic parameters (using a force platform and the optoelectronic system) in 20 normal subjects. Two conditions: 1) self-generated initiation; and 2) initiation triggered by a "beep" sound were studied to evaluate the APA phase, by recording kinetic data (duration of the APAs, trajectory of the center of pressure, speed and trajectory of the center of mass). Kinematic data (first and second step speed, length and duration) were also recorded. RESULTS: First step speed and length were increased in self-paced gait initiation compared to triggered gait initiation in controls. We found no difference between the 2 conditions in terms of second step kinematic data. It was caused by a significant difference between the 2 conditions for the temporal characteristics of anticipatory postural adjustments (APAs) in the initiation of the first step, which was longer when normal subjects performed self-generated gait initiation. The trajectory of center of pressure and center of mass remained the same in the 2 conditions. CONCLUSION: APAs of gait initiation process are delayed under self-paced condition, although they do not differ qualitatively between reaction time and self-paced condition. Neuphysiological support of self-generated movement could explain these differences.


Subject(s)
Gait/physiology , Posture/physiology , Acoustic Stimulation , Adult , Biomechanical Phenomena , Female , Humans , Male , Middle Aged , Reaction Time , Walking/physiology
11.
Bone Marrow Transplant ; 28(4): 405-7, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11571515

ABSTRACT

Recombinant factor VIIa (rFVIIa, NovoSeven) is FDA-approved for the treatment of bleeding in patients with hemophilia A/B with inhibitors. A growing literature suggests that there may be expanded indications for the use of NovoSeven in patients with significant bleeding who do not have a known factor deficiency. Severe bleeding refractory to standard hematologic or hemostatic support is common in patients undergoing bone marrow transplantation (BMT). We review our experience with rFVIIa in three patients (8 years 8 months to 19 years, median 13 years) treated for pulmonary hemorrhage (n = 1), hemorrhagic cystitis (n = 3), and gastrointestinal bleeding (n = 2). Boluses of 90-270 microg/kg rVIIa with subsequent doses of 90 microg/kg every 4-24 h for 3-14 days were given, concurrent with maintaining platelet counts >50,000/mm(3). Transient clinical responses in gross hematuria (two patients) and in pulmonary hemorrhage were noted within several days of starting rFVIIa, but bleeding in a new site in two patients and renewed bleeding of the initial site in the third resulted in discontinuation of the drug. No toxicity or adverse events were observed while the patients were on rFVIIa treatment. Because of the substantial cost of this product, the lack of adequate monitoring methodology, and the variability of current dose and dosing intervals, large randomized studies are needed before definitive off-label use in the setting of BMT can be recommended.


Subject(s)
Bone Marrow Transplantation/methods , Factor VII/therapeutic use , Recombinant Proteins/therapeutic use , Acute Disease , Adolescent , Adult , Anemia, Aplastic/complications , Anemia, Aplastic/therapy , Bone Marrow Transplantation/adverse effects , Child , Factor VIIa , Female , Hemorrhage/drug therapy , Humans , Leukemia, Myeloid/complications , Leukemia, Myeloid/therapy , Retrospective Studies
12.
J Exp Biol ; 204(Pt 15): 2709-16, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11533121

ABSTRACT

Previous investigations of haemolymph sugar levels in honeybees have reported very different results, probably because different experimental conditions affected the activity levels of the animals. The present study investigated the dependence of haemolymph sugar levels in foraging honeybees on metabolic rate and whether the haemolymph sugar level is regulated. Free-flying foraging bees were trained to collect controlled amounts of sucrose solution of different concentrations (15%, 30% or 50% sucrose w/w). Immediately after feeding, metabolic rate was measured over a given time depending on the sucrose concentration, then crop-emptying rate and haemolymph sugar levels were measured. Bees exhibiting a wide range of metabolic rates were compared to establish whether the observed differences in haemolymph sugar levels were due to limits in the supply of sugars from the crop or in the rate of trehalose synthesis in the fat bodies. Independent of the concentration of the sucrose solution supplied, haemolymph trehalose, glucose and fructose levels were constant for metabolic rates from 0 to 4.5 ml CO(2)h(-1). At higher metabolic rates, trehalose concentration decreased while that of glucose and fructose increased, with the exception of bees fed 15% sucrose solution. As the supply of sugar from the crop via the proventriculus was sufficient to support even the highest metabolic rates, the observed pattern must result from an upper limit in the capacity of the fat body to synthesise trehalose. The maximal rate of conversion of glucose to trehalose in the fat body was therefore calculated to average 92.4 microg glucosemin(-1). However, for bees fed 15% sucrose solution both the rate of conversion of glucose to trehalose and the rate of sugar transport from the crop to the ventricle were limited, together resulting in a decrease in total haemolymph sugar levels for metabolic rates higher than 5 ml CO(2)h(-1).


Subject(s)
Basal Metabolism , Bees/metabolism , Hemolymph/chemistry , Polysaccharides/blood , Trehalose/biosynthesis , Animals , Dietary Sucrose/administration & dosage , Fat Body/metabolism , Fructose/analysis , Glucose/analysis , Kinetics , Trehalose/analysis
13.
Am J Epidemiol ; 154(2): 106-14, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11447042

ABSTRACT

To evaluate the effects of parental occupational chemical exposures on incidence of neuroblastoma in offspring, the authors conducted a multicenter case-control study, using detailed exposure information that allowed examination of specific chemicals. Cases were 538 children aged 19 years who were newly diagnosed with confirmed neuroblastoma in 1992-1994 and were registered at any of 139 participating hospitals in the United States and Canada. One age-matched control for each of 504 cases was selected through random digit dialing. Self-reported exposures were reviewed by an industrial hygienist, and improbable exposures were reclassified. Effect estimates were calculated using unconditional logistic regression, adjusting for child's age and maternal demographic factors. Maternal exposures to most chemicals were not associated with neuroblastoma. Paternal exposures to hydrocarbons such as diesel fuel (odds ratio (OR) = 1.5; 95% confidence interval (CI): 0.8, 2.6), lacquer thinner (OR = 3.5; 95% CI: 1.6, 7.8), and turpentine (OR = 10.4; 95% CI: 2.4, 44.8) were associated with an increased incidence of neuroblastoma, as were exposures to wood dust (OR = 1.5; 95% CI: 0.8, 2.8) and solders (OR = 2.6; 95% CI: 0.9, 7.1). The detailed exposure information available in this study has provided additional clues about the role of parental occupation as a risk factor for neuroblastoma.


Subject(s)
Hazardous Substances/adverse effects , Maternal Exposure/adverse effects , Neuroblastoma/chemically induced , Neuroblastoma/epidemiology , Occupational Exposure/adverse effects , Paternal Exposure/adverse effects , Adolescent , Canada/epidemiology , Case-Control Studies , Child , Child, Preschool , Dust , Environmental Monitoring , Epidemiological Monitoring , Female , Hazardous Substances/analysis , Humans , Hydrocarbons/adverse effects , Incidence , Infant , Infant, Newborn , Lacquer/adverse effects , Logistic Models , Male , Neuroblastoma/diagnosis , Occupational Exposure/analysis , Population Surveillance , Registries , Risk Factors , Surveys and Questionnaires , Turpentine/adverse effects , United States/epidemiology , Wood
15.
Am J Epidemiol ; 153(12): 1227-32, 2001 Jun 15.
Article in English | MEDLINE | ID: mdl-11415959

ABSTRACT

In epidemiologic studies, much of the variation in disease risk estimates associated with occupational pesticide exposure may be due to variation in exposure classification. The authors compared five different methods of using interview information to assess occupational pesticide exposure in a US-Canada case-control study of neuroblastoma (1992-1994). For each method, exposure assignment was compared with that of a reference method, and neuroblastoma effect estimates were calculated. Compared with the reference method, which included a complete review of occupation, industry, job tasks, and exposure-specific activities, the use of occupation-industry groups alone or in combination with general job task information diluted the exposed group by including individuals who were unlikely to have been truly exposed. The effect estimates representing associations between each exposure method and neuroblastoma were different enough to influence the study's conclusions, especially when the exposure was rare (for maternal occupational pesticide exposure, the odds ratio was 0.7 using the reference exposure assessment method and 3.2 using the occupation-industry group exposure assessment method). Exposure-specific questions about work activities can help investigators distinguish truly exposed individuals from those who report exposure but are unlikely to have been exposed above background levels and from those who have not been exposed but are misclassified as exposed because of their employment in an occupation-industry group determined a priori to be exposed.


Subject(s)
Maternal Exposure , Neuroblastoma/chemically induced , Neuroblastoma/epidemiology , Occupational Exposure , Paternal Exposure , Pesticides , Adult , Canada/epidemiology , Case-Control Studies , Child , Child, Preschool , Female , Humans , Infant , Interviews as Topic , Logistic Models , Male , Predictive Value of Tests , Risk Assessment , Sensitivity and Specificity , United States/epidemiology
16.
Pediatr Transplant ; 5(2): 125-31, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11328551

ABSTRACT

To define the incidence, course, and etiology of hematologic abnormalities in children on tacrolimus-based immunosuppression, we reviewed records of 106 transplant patients (70 heart, 16 heart and lung, 20 double lung), 0-21 yr of age, who were transplanted at the Children's Hospital of Pittsburgh from 1989 to 1997. Fifty-four of the 106 patients (51%) developed 65 abnormal hematologic episodes (32 anemia, nine neutropenia, nine thrombocytopenia, 15 simultaneous anemia and neutropenia with or without thrombocytopenia). Common etiologies included: infections, post-transplant lymphoproliferative disease, and medications. Eleven episodes (seven anemia, one neutropenia, and three simultaneous anemia and neutropenia) had unclear etiologies and process of elimination suggested an association with tacrolimus. Interventions included filgrastim (effective in 15 of 15 patients, with resolution of neutropenia in a median of 5 days) and epoetin alfa (effective in five of 16 patients, including four of four patients with anemia possibly related to tacrolimus). Five patients (two with neutropenia and three with simultaneous neutropenia and anemia) were switched to cyclosporin A (CsA); rapid resolution occurred in four of the five patients, suggesting a possible association of the hematologic abnormalities with tacrolimus. In summary, hematologic abnormalities are common in children on tacrolimus-based immunosuppression. Most of these hematologic abnormalities are caused by common etiologies; however, a sub-population exists where tacrolimus may be the etiologic agent. Anemia and neutropenia respond to treatment with epoetin alfa and filgrastim. After thorough investigation, a trial switch to CsA may be warranted.


Subject(s)
Heart Transplantation , Hematologic Diseases/etiology , Immunosuppressive Agents/therapeutic use , Lung Transplantation , Tacrolimus/therapeutic use , Adolescent , Adult , Anemia/etiology , Child , Child, Preschool , Epoetin Alfa , Erythropoietin/therapeutic use , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/therapeutic use , Heart Transplantation/adverse effects , Heart Transplantation/immunology , Heart-Lung Transplantation/adverse effects , Heart-Lung Transplantation/immunology , Humans , Infant , Lung Transplantation/adverse effects , Lung Transplantation/immunology , Male , Neutropenia/drug therapy , Neutropenia/etiology , Recombinant Proteins , Retrospective Studies , Thrombocytopenia/etiology
17.
J Pediatr Hematol Oncol ; 23(1): 30-8, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11196267

ABSTRACT

PURPOSE: The objectives of this study were: 1) to compare the time to hematologic recovery (absolute neutrophil count [ANC] > or = 1,000/mm3 and platelet count > or = 100,000/mm3) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 microg/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response [CR] + partial response [PR]) of ICE in children with refractory or recurrent solid tumors. PATIENTS AND METHODS: From June 1992 until November 1994, 123 patients with recurrent or refractory pediatric solid tumors were treated with ifosfamide (1,800 mg/m2 per day x 5), carboplatin (400 mg/m2 per day x 2), and etoposide (100 mg/m2 per day x 5) and randomized to receive either 5.0 microg/kg per day or 10.0 microg/kg per day of G-CSF subcutaneously until recovery of ANC to > or = 1,000/mm3. RESULTS: The incidence of grade 4 neutropenia during the first course was 88%. Median time from the start of chemotherapy to ANC > or = 1,000/mm(-3) for all patients during courses 1 and 2 was 21 and 19 days, respectively. The incidence of developing platelet count < or = 20,000/mm3 during course 1 was 82%. The median time from the start of the course of chemotherapy to platelet recovery > or =100,000/mm3 for all patients during courses 1 and 2 was 27 days. There was no significant difference in the median time of ANC recovery, platelet recovery, or incidence of grade 4 neutropenia; and in the median days of fever and the incidence of infections requiring hospitalization and intravenous antibiotics during courses 1 and 2, there was no significant difference between the two doses of G-CSF. One hundred eighteen patients were evaluated for response to ICE. The overall response rate (CR + PR) in this study was 51% (90% confidence interval, 43%-59%). The CR rate for all diagnostic categories was 27%. The Kaplan-Meier estimates of 1-year and 2-year survival probabilities for all patients were 52% and 30%, respectively. CONCLUSION: In summary, this combination of chemotherapy (ICE) was associated with a high CR rate (27%) in children with recurrent or refractory solid tumors, but also with a high incidence of grade 4 neutropenia and thrombocytopenia. Doubling the dose of G-CSF from 5.0 to 10.0 microg/kg per day after ICE chemotherapy did not result in an enhancement of neutrophil or platelet recovery or the incidence of grade 4 neutropenia developing.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Neoplasms/drug therapy , Neutropenia/etiology , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Child , Child, Preschool , Dose-Response Relationship, Drug , Etoposide/administration & dosage , Female , Humans , Ifosfamide/administration & dosage , Infant , Leukocyte Count , Male , Neoplasms/mortality , Neutropenia/prevention & control , Neutrophils , Prospective Studies , Racial Groups , Recombinant Proteins , Recurrence , Survival Rate , Time Factors , United States
19.
Epidemiology ; 12(1): 20-7, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11138814

ABSTRACT

Neuroblastoma is the most common neoplasm in children under 1 year of age. We examined the relation between residential exposure to pesticides and neuroblastoma, using data from a case-control study of risk factors for neuroblastoma. Incident cases of neuroblastoma (N = 538) were identified through the Pediatric Oncology Group and the Children's Cancer Group. One age-matched control was identified for each case by random digit dialing. Telephone interviews with each parent collected information on residential exposure to pesticides. Pesticide use in both the home and garden were modestly associated with neuroblastoma [odds ratio (OR) = 1.6 (95% confidence interval [95% CI] = 1.0-2.3, and OR = 1.7 (95% CI = 0.9-2.1), respectively]. Compared with infants [OR = 1.0 (95% CI = 0.6-2.0)], stronger associations were found for garden pesticides in children diagnosed after 1 year of age [OR = 2.2 (95% CI = 1.3-3.6)], which suggests that pesticides may act through a mechanism more common for neuroblastomas in older children. There was no evidence of differential pesticide effects in subgroups of neuroblastoma defined by MYCN oncogene amplification or tumor stage.


Subject(s)
Environmental Exposure/adverse effects , Neoplasms/chemically induced , Neuroblastoma/chemically induced , Pesticides/adverse effects , Canada/epidemiology , Case-Control Studies , Child, Preschool , Humans , Infant , Infant, Newborn , Neoplasms/epidemiology , Neuroblastoma/epidemiology , Odds Ratio , Risk Factors , United States/epidemiology
20.
J Neurol ; 248(11): 944-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11757957

ABSTRACT

Chronic bilateral internal globus pallidus (GPi) stimulation allows control of levodopa induced dyskinesias (LID) and motor symptoms in severe Parkinson's disease (PD). The effect on gait has not been clearly established. Different results have been reported, mostly consisting of clinical data. The aim of this study was to evaluate, by means of a video motion analysis system (optoelectronic VICON system), the influence of bilateral GPi stimulation on gait in PD. Five patients underwent bilateral GPi stimulation. The preoperative and postoperative (3 months after surgery) clinical gait disturbances (items 29 and 30 of the motor UPDRS), as well as spatial and temporal gait measurements (namely cadence, velocity, stride and step times, single and double limb support times, stride and step lengths) were analysed in off condition (the patient had received no treatment for 12 hours or merely the lowest dose of levodopa allowing him to walk for the gait analysis) and in the on drug condition (after administration of 200 mg of levodopa). The gait analysis was performed with the VICON system. In off condition, there was a statistically significant improvement after surgery for UPDRS III and gait (clinically assessed). In on drug condition, there was a significant improvement for LID whereas UPDRS III and clinical assessment of gait were unchanged. The VICON system also showed that surgery improved gait especially in off condition, but also in on drug condition. Our method allowed exact quantification of the influence of surgery on gait characteristics. As compared with levodopa treatment, the effect of stimulation seems to be different. Indeed, the results suggest only limited effects of pallidal stimulation on the control of stride length and rather point to compensatory additional mechanisms.


Subject(s)
Antiparkinson Agents/pharmacology , Dyskinesias/etiology , Electric Stimulation Therapy , Gait , Globus Pallidus/physiology , Levodopa/pharmacology , Parkinson Disease/therapy , Aged , Female , Humans , Kinetics , Male , Middle Aged , Severity of Illness Index , Treatment Outcome
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