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Showing papers by "Rush University Medical Center published in 1998"


Journal ArticleDOI
TL;DR: Biopsy of sentinel nodes can predict the presence or absence of axillary-node metastases in patients with breast cancer, however, the procedure can be technically challenging, and the success rate varies according to the surgeon and the characteristics of the patient.
Abstract: Background Pilot studies indicate that probe-guided resection of radioactive sentinel nodes (the first nodes that receive drainage from tumors) can identify regional metastases in patients with breast cancer. To confirm this finding, we conducted a multicenter study of the method as used by 11 surgeons in a variety of practice settings. Methods We enrolled 443 patients with breast cancer. The technique involved the injection of 4 ml of technetium-99m sulfur colloid (1 mCi [37 MBq]) into the breast around the tumor or biopsy cavity. “Hot spots” representing underlying sentinel nodes were identified with a gamma probe. Sentinel nodes subjacent to hot spots were removed. All patients underwent a complete axillary lymphadenectomy. Results The overall rate of identification of hot spots was 93 percent (in 413 of 443 patients). The pathological status of the sentinel nodes was compared with that of the remaining axillary nodes. The accuracy of the sentinel nodes with respect to the positive or negative status o...

1,923 citations


Journal ArticleDOI
27 May 1998-JAMA
TL;DR: Experimental animal models suggest that statins may foster stability through a reduction in macrophages and cholesterol ester content and an increase in volume of collagen and smooth muscle cells, which help to explain the early and significant cardiovascular event reduction reported in several clinical trials of statin therapy.
Abstract: Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin therapy have demonstrated that baseline or treated low-density lipoprotein (LDL) cholesterol levels are only weakly associated with net coronary angiographic change or cardiovascular events. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation. Experimental animal models suggest that statins may foster stability through a reduction in macrophages and cholesterol ester content and an increase in volume of collagen and smooth muscle cells. The thrombotic sequelae caused by plaque disruption is mitigated by statins through inhibition of platelet aggregation and maintenance of a favorable balance between prothrombotic and fibrinolytic mechanisms. These nonlipid properties of statins may help to explain the early and significant cardiovascular event reduction reported in several clinical trials of statin therapy.

974 citations


Journal ArticleDOI
TL;DR: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures and represents the advent of a new, nonpharmacologic treatment for epilepsy.
Abstract: Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

910 citations


Journal ArticleDOI
TL;DR: This review focuses on electrochemical corrosion phenomena in alloys used for orthopaedic implants, evidenced by particulate corrosion and wear products in tissue surrounding the implant, which may ultimately result in a cascade of events leading to periprosthetic bone loss.
Abstract: In situ degradation of metal-alloy implants is undesirable for two reasons: the degradation process may decrease the structural integrity of the implant, and the release of degradation products may elicit an adverse biological reaction in the host Degradation may result from electrochemical dissolution phenomena, wear, or a synergistic combination of the two Electrochemical processes may include generalized corrosion, uniformly affecting the entire surface of the implant, and localized corrosion, affecting either regions of the device that are shielded from the tissue fluids (crevice corrosion) or seemingly random sites on the surface (pitting corrosion) Electrochemical and mechanical processes (for example, stress corrosion cracking, corrosion fatigue, and fretting corrosion) may interact, causing premature structural failure and accelerated release of metal particles and ions The clinical importance of degradation of metal implants is evidenced by particulate corrosion and wear products in tissue surrounding the implant, which may ultimately result in a cascade of events leading to periprosthetic bone loss Furthermore, many authors have reported increased concentrations of local and systemic trace metal in association with metal implants1,4,5,9-11,14,18,25,26,28,29,47,49-55,58,71,72,75-77,87,90,108-110 There also is a low but finite prevalence of corrosion-related fracture of the implant This review focuses on electrochemical corrosion phenomena in alloys used for orthopaedic implants A summary of basic electrochemistry is followed by a discussion of retrieval studies of the response of the implant to the host environment and the response of local tissue to implant corrosion products The systemic implications of the release of metal particles also are presented Finally, future directions in biomaterials research and development …

908 citations


Journal ArticleDOI
TL;DR: There is a significant relationship between the adduction moment and OA disease severity and serum hyaluronan levels correlate with joint space width but not with theAdduction moment.
Abstract: Objective The adduction moment at the knee during gait is the primary determinant of medial-tolateral load distribution. If the adduction moment contributes to progression of osteoarthritis (OA), then patients with advanced medial tibiofemoral OA should have higher adduction moments. The present study was undertaken to investigate the hypothesis that the adduction moment normalized for weight and height is associated with medial tibiofemoral OA disease severity after controlling for age, sex, and pain level, and to examine the correlation of serum hyaluronan (HA) level with disease severity and with the adduction moment in a subset of patients. Methods Fifty-four patients with medial tibiofemoral OA underwent gait analysis and radiographic evaluation. Disease severity was assessed using the Kellgren-Lawrence (K-L) grade and medial joint space width. In a subset of 23 patients with available sera, HA was quantified by sandwich enzyme-linked immunosorbent assay. Pearson correlations, a random effects model, and multivariate regression models were used. Results The adduction moment correlated with the K-L grade in the left and right knees (r = 0.68 and r = 0.60, respectively), and with joint space width in the left and right knees (r = -0.45 and r = -0.47, respectively). The relationship persisted after controlling for age, sex, and severity of pain. The partial correlation between K-L grade and adduction moment was 0.71 in the left knees and 0.61 in the right knees. For every 1.0-unit increase in adduction moment, there was a 0.63-mm decrease in joint space width. In the subset of patients in whom serum HA levels were measured, HA levels correlated with medial joint space width (r = -0.55), but not with the adduction moment. Conclusion There is a significant relationship between the adduction moment and OA disease severity. Serum HA levels correlate with joint space width but not with the adduction moment. Longitudinal studies will be necessary to determine the contribution of the adduction moment, and its contribution in conjunction with metabolic markers, to progression of medial tibiofemoral OA.

703 citations


Journal ArticleDOI
TL;DR: In this article, the effects of long-term therapy (i.e., for more than one year) with intravenous epoprostenol (prostacyclin) in patients with advanced primary pulmonary hypertension was evaluated.
Abstract: Background Primary (idiopathic) pulmonary hypertension is a progressive, fatal disease. Conventional therapy with anticoagulant and vasodilator drugs may improve symptoms and survival among selected patients, but there is no evidence that the disease can be reversed. Methods We evaluated the effects of long-term therapy (i.e., for more than one year) with intravenous epoprostenol (prostacyclin) in patients with advanced primary pulmonary hypertension. The base-line evaluation included an assessment of pulmonary vascular dilation in response to intravenous adenosine. The epoprostenol dose was increased monthly to the maximum tolerated. Long-term therapy was evaluated by measuring improvement in symptoms, exercise capacity, and hemodynamic variables. Results We evaluated 27 patients with primary pulmonary hypertension over a mean (±SD) period of 16.7±5.2 months. Intravenous adenosine had a variable effect on pulmonary vascular resistance (mean reduction, 27 percent; range, 0 to 56; P<0.001). Epoprostenol th...

620 citations


Journal ArticleDOI
01 May 1998-Stroke
TL;DR: These data support the presence of a circadian pattern in the onset of stroke, with a significantly higher risk in the morning.
Abstract: Background and Purpose—Acute myocardial infarction and sudden death display a circadian rhythm, with a higher risk between 6 am and noon. Some reports suggest that stroke does not follow such a circadian variation and that hemorrhagic stroke occurs more often during the evening. Methods—A meta-analysis of 31 publications reporting the circadian timing of 11 816 strokes was performed, subdividing (when possible) by the type of stroke, according to the time of onset of symptoms. When precise timing was not given, strokes were distributed evenly (that is, biasing toward the null hypothesis of lack of circadian variation). Results—All subtypes of strokes displayed a significant (P<0.001) circadian variation in time of onset, whether divided into 3-, 4-, or 6-hour time periods. There was a 49% increase (95% confidence interval, 44% to 55%) in stroke of all types between 6 am and noon (compared with expectations if no circadian variation was present), which is a 79% (95% confidence interval, 72% to 87%) increas...

588 citations


Journal ArticleDOI
TL;DR: Substitution of MMF for azathioprine may reduce mortality and rejection in the first year after cardiac transplantation.
Abstract: BACKGROUND After heart transplantation, 1-year and 5-year survival rates are 79% and 63%, respectively, with rejection, infection, and allograft coronary artery disease accounting for the majority of deaths. Mycophenolate mofetil (MMF), an inhibitor of the de novo pathway for purine biosynthesis, decreases rejection in animals and in human renal transplantation. METHODS In a double-blind, active-controlled trial, 28 centers randomized 650 patients undergoing their first heart transplant to receive MMF (3000 mg/day) or azathioprine (1.5-3 mg/kg/day), in addition to cyclosporine and corticosteroids. Rejection and survival data were obtained for 6 and 12 months, respectively. Because 11% of the patients withdrew before receiving study drug, data were analyzed on all randomized patients (enrolled patients) and on patients who received study medications (treated patients). RESULTS Survival and rejection were similar in enrolled patients (MMF, n=327; azathioprine, n=323). In treated patients (MMF, n=289; azathioprine, n=289), the MMF group compared with the azathioprine group was associated with significant reduction in mortality at 1 year (18 [6.2%] versus 33 deaths [11.4%]; P=0.031) and a significant reduction in the requirement for rejection treatment (65.7% versus 73.7%; P=0.026). There was a trend for fewer MMF patients to have > or = grade 3A rejection (45.0% versus 52.9%; P=0.055) or require the murine monoclonal anti-CD3 antibody or antithymocyte globulin (15.2% versus 21.1%; P=0.061). Opportunistic infections, mostly herpes simplex, were more common in the MMF group (53.3% versus 43.6%; P=0.025). CONCLUSIONS Substitution of MMF for azathioprine may reduce mortality and rejection in the first year after cardiac transplantation.

579 citations


Journal ArticleDOI
TL;DR: It is suggested that fretting corrosion at the head-neck coupling is an important source of metal release that can lead to increased concentrations of chromium in the serum and urine after total hip replacement.
Abstract: There is an increasing recognition that, in the long term, total joint replacement may be associated with adverse local and remote tissue responses that are mediated by the degradation products of prosthetic materials. Particular interest has centered on the metal-degradation products of total joint

571 citations


Journal ArticleDOI
TL;DR: APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.
Abstract: Background The e4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. Methods We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE e4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. Results Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of ...

503 citations


Journal ArticleDOI
01 Jul 1998-Immunity
TL;DR: The Wiskott-Aldrich syndrome is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton, and WASP function is implicated in receptor signaling and cytoskeletal reorganization in T and B cells.

Journal Article
TL;DR: Although severe angiographic allograft coronary artery disease occurs in only 7% of the patients at 5 years, its presence is highly predictive of subsequent coronary artery Disease-related events or retransplantation.
Abstract: Background: Controversy exists regarding donor and recipient factors that promote the development and progression of coronary artery disease after heart transplantation and the likelihood of coronary artery disease causing death or retransplantation Methods: To investigate this issue in a large cohort of patients, we analyzed 5963 postoperative angiograms performed in 2609 of the 3837 patients undergoing heart transplantation at 39 institutions between January 1990 and December 1994 Coronary artery disease was classified as mild, moderate, or severe on the basis of left main involvement, primary vessel stenoses, and branch stenoses Coronary artery disease was considered severe if left main stenosis was > 70% or 2 or more primary vessels stenoses were > 70% or branch stenoses were > 70% in all 3 systems Results: By the end of 5 years after heart transplantation, coronary artery disease was present in 42% of the patients, mild in 27%, moderate in 8%, and severe in 7% Coronary artery disease-related events (death or retransplantation) had an actuarial incidence of 7% at 5 years and occurred in 2 of 3 of the patients with development of angiographically severe coronary artery disease By multivariable logistic analysis, risk factors for donor coronary artery disease included older donor age (P <0001) and donor hypertension (P =0002) By multivariable analysis in the hazard function domain, risk factors identified for the earlier onset of allograft coronary artery disease included older donor age (P <0001), donor male sex (P =0006), donor hypertension (P =07), recipient male sex (P =02), and recipient black race (P =01 ) The actuarial incidence of severe coronary artery disease was 9% at 5 years Conclusions: Angiographic coronary artery disease is very common after heart transplantation, occurring in approximately 42% of the patients by 5 years Older donor age, donor hypertension, and male donor or recipient predict earlier onset of angiographic allograft coronary artery disease Although severe angiographic allograft coronary artery disease occurs in only 7% of the patients at 5 years, its presence is highly predictive of subsequent coronary artery disease-related events or retransplantation J Heart Lung Transplant 1998;17:744-53

Journal ArticleDOI
15 Sep 1998-Cancer
TL;DR: This report presents the results of a survival update based on the combined data from two studies that compared the efficacy and tolerability of anastrozole (1 or 10 mg once daily) and megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma whose disease had progressed after treatment with tamoxifen.
Abstract: BACKGROUND. This report presents the results of a survival update based on the combined data from two studies that compared the efficacy and tolerability of anastrozole (1 or 10 mg once daily), a selective, nonsteroidal aromatase inhibitor administered orally, and megestrol acetate (40 mg 4 times daily) in the treatment of postmenopausal women with advanced breast carcinoma whose disease had progressed after treatment with tamoxifen. METHODS. Two randomized, parallel-group, multicenter trials were conducted, involving a total of 764 patients. The two trials were identical in design; both were double blind for anastrozole and open label for megestrol acetate. Overview analyses were conducted with the intent of strengthening the interpretation of results from each trial. The median follow-up duration for this survival update was 31 months. RESULTS. At the clinical dose of 1 mg daily, anastrozole demonstrated a statistically significant survival advantage over megestrol acetate, with a hazard ratio of 0.78 (P , 0.025)(0.60 , 97.5% confidence interval [CI] ,1.0). The 1 mg anastrozole group also had a longer median time to death (26.7 months) compared with 22.5 months for the megestrol acetate group. The 10 mg anastrozole group also had a survival benefit over the megestrol acetate group, with a hazard ratio of 0.83 (P 5 0.09, not significant)(0.64 , 97.5% CI , 1.1). Higher 2-year survival rates were observed for both anastrozole treatment groups than for the megestrol acetate group (56.1%, 54.6%, and 46.3% for the groups given 1 mg anastrozole, 10 mg anastrozole, and megestrol acetate, respectively).

Journal ArticleDOI
01 Sep 1998-Chest
TL;DR: Digoxin produces a modest increase in cardiac output in patients with pulmonary hypertension and right ventricular failure, as well as a significant reduction in circulating norepinephrine, and no detectable effects of digoxin on baroreceptor responsiveness were apparent.

Journal ArticleDOI
TL;DR: The post-operative physical examination and KT-1000 arthrometer results were statistically improved when compared with preoperative findings, and the Tegner activity level was significantly improved from prereconstruction ratings and similar to preinjury ratings.
Abstract: We retrospectively reviewed the results of 97 patients with anterior cruciate ligament reconstructions using an arthroscopically assisted two-incision technique without extraarticular augmentation at an intermediate followup of 5 to 9 years postoperatively. Evaluation included detailed history, physical examination, functional testing, KT-1000 arthrometer measurements, multiple scoring systems, and radiographs. The results were compared with those from a previous study that evaluated a smaller patient cohort using the identical surgical technique at a 2- to 4-year followup. The post-operative physical examination and KT-1000 arthrometer results were statistically improved when compared with preoperative findings. A negative pivot shift result was noted in 83% of patients, and a 1 result in 17% of patients. Seventy percent of patients had 3 mm difference on manual maximum side-to-side testing. Functional testing averaged less than 2% asymmetry for vertical jump, single-legged hop, or timed 6-meter hop. The...

Journal ArticleDOI
TL;DR: Bright light therapy had a specific antidepressant effect beyond its placebo effect, but it took at least 3 weeks for a significant effect to develop, and it took more of the complete or almost complete remissions than placebo.
Abstract: Background Bright light therapy is the recommended treatment for winter seasonal affective disorder (SAD). However, the studies with the best placebo controls have not been able to demonstrate that light treatment has a benefit beyond its placebo effect. Methods Ninety-six patients with SAD completed the study. Patients were randomly assigned to 1 of 3 treatments for 4 weeks, each 1.5 hours per day: morning light (average start time about 6 AM), evening light (average start about 9 PM), or morning placebo (average start about 6 AM). The bright light (≈6000 lux) was produced by light boxes, and the placebos were sham negative-ion generators. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) were performed weekly. Results There were no differences among the 3 groups in expectation ratings or mean depression scores after 4 weeks of treatment. However, strict response criteria revealed statistically significant differences; after 3 weeks of treatment morning light produced more of the complete or almost complete remissions than placebo. By 1 criterion (24-item SIGH-SAD score Conclusions Bright light therapy had a specific antidepressant effect beyond its placebo effect, but it took at least 3 weeks for a significant effect to develop. The benefit of light over placebo was in producing more of the full remissions.

Journal ArticleDOI
TL;DR: It is suggested that use of the higher-dose vitamin E and vitamin C supplements may lower the risk of Alzheimer disease.
Abstract: Oxidative stress may play a role in neurologic disease. The present study examined the relation between use of vitamin E and vitamin C and incident Alzheimer disease in a prospective study of 633 persons 65 years and older. A stratified random sample was selected from a disease-free population. At baseline, all vitamin supplements taken in the previous 2 weeks were identified by direct inspection. After an average follow-up period of 4.3 years, 91 of the sample participants with vitamin information met accepted criteria for the clinical diagnosis of Alzheimer disease. None of the 27 vitamin E supplement users had Alzheimer disease compared with 3.9 predicted based on the crude observed incidence among nonusers (p = 0.04) and 2.5 predicted based on age, sex, years of education, and length of follow-up interval (p = 0.23). None of the 23 vitamin C supplement users had Alzheimer disease compared with 3.3 predicted based on the crude observed incidence among nonusers (p = 0.10) and 3.2 predicted adjusted for age, sex, education, and follow-up interval (p = 0.04). There was no relation between Alzheimer disease and use of multivitamins. These data suggest that use of the higher-dose vitamin E and vitamin C supplements may lower the risk of Alzheimer disease.

Journal ArticleDOI
TL;DR: It has long been suggested that the adduction moment is the primary determinate of the distribution of load between the medial and lateral plateaus, but this is the first evidence of its relationship to the underlying bone distribution.

Journal ArticleDOI
TL;DR: The proposed technique, cross-recurrence quantification, demonstrates the ability to extract signals up to a very low signal-to-noise-ratio and to allow an immediate appreciation of their degree of periodicity.

Journal ArticleDOI
TL;DR: Parallels between the function of hematopoietic cytokines in bone marrow and the central nervous system may exist and be useful in understanding the factors which regulate the differentiation of neurons in the brain.

Journal Article
TL;DR: The results suggest that cell growth inhibition by IFN-gamma is due to apoptosis mediated by Fas and FasL interaction.
Abstract: The mechanism by which IFN-gamma inhibits tumor cell growth has not been fully understood. Here we report that IFN-gamma up-regulated the expression of Fas and Fas ligand (FasL) on HT29 cells, a human colon adenocarcinoma cell line, and subsequently induced apoptosis of these cells. The kinetics of cell death in IFN-gamma-treated HT29 cells paralleled the increase in the levels of Fas and FasL expression. We further show that IFN-gamma up-regulated the expression of Fas and FasL in STAT1-transfected U3A cells but not in STAT1-deficient U3A cells. Correspondingly, IFN-gamma induced cell death in STAT1-transfected U3A cells but not in STAT1-deficient U3A cells. IFN-gamma-induced cell death was inhibited by caspase-1 inhibitors. Our results suggest that cell growth inhibition by IFN-gamma is due to apoptosis mediated by Fas and FasL interaction.

Journal ArticleDOI
TL;DR: These data provide essential confirmation that, under appropriate transplant conditions, grafted nigral neurons can survive, reinnervate the host striatum, and provide clinical benefit to PD patients and support the concept that improved motor function and striatal FD uptake on PET after nigral grafting in PD are the result of the viability of grafted neurons and graft‐derived reinnervation of the host stripping.
Abstract: We have previously demonstrated that fetal nigral grafts can survive, reinnervate the striatum, and mediate clinically relevant recovery in a patient with Parkinson's disease (PD). Most previous autopsy cases have failed to identify meaningful numbers of viable grafted cells suggesting that differences in critical transplant variables determine graft viability. The present study evaluated the structural and functional correlates of fetal nigral transplantation in a second PD patient who received fetal nigral grafts according to our previously published transplant protocol. A 61-year-old woman with severe PD received bilateral fetal nigral grafts to the postcommissural putamen from seven donor fetuses (four right side and three left side) aged 6.5-9 weeks postconception. This patient died 19 months after surgery from a cause unrelated to the transplant surgery. Her postoperative clinical course was characterized by improved motor and activities of daily living scores during "off time," reduced "off time," and increased "on" time without dyskinesia. Positron emission tomography (PET) scans revealed a bilateral and progressive increase in fluorodopa (FD) uptake within the grafted putamen. Postmortem examination of the right hemisphere revealed large oval-shaped grafts containing more than 138,000 tyrosine-hydroxylase-immunoreactive (TH-ir) neurons. Grafted cells formed a seamless border with the host and provided dense TH-ir innervation to 78% of the host postcommissural putamen. Graft-mediated sprouting of host fibers was not observed. These data provide essential confirmation that, under appropriate transplant conditions, grafted nigral neurons can survive, reinnervate the host striatum, and provide clinical benefit to PD patients. These findings also support the concept that improved motor function and striatal FD uptake on PET after nigral grafting in PD are the result of the viability of grafted neurons and graft-derived reinnervation of the host striatum.

Journal ArticleDOI
TL;DR: The correlation of motor deficits with the loss of TH‐ir and DAT‐ir nigral neurons suggests that aged nonhuman primates may provide a useful model for mimicking changes seen in human aging and early Parkinson's disease.
Abstract: Although the role of dopamine dysfunction is well established in Parkinson's disease, the effect of nigrostriatal degeneration on motor performance during normal aging is less well understood. In this study, aged rhesus monkeys (25-27 years old) displayed significant impairments relative to young (3-5 years old) cohorts in motor function as assessed on a fine motor task and home cage activity. Additionally, the clinical motor function of aged monkeys was impaired relative to young monkeys as assessed on a clinical rating scale. Unbiased stereologic measurements of the substantia nigra revealed a significant age-related loss of tyrosine hydroxylase-immunoreactive (TH-ir; 50.3%) and dopamine transporter-immunoreactive (DAT-ir; 33.2%) nigral neurons. The monkeys performance on the fine motor task and on the clinical rating scale was correlated with TH-ir neuronal counts. The number of DAT-ir nigral neurons was correlated with activity and clinical rating scale scores. Our results suggest that age-related motor impairments in nonhuman primates are associated with spontaneous decreases in TH-ir and DAT-ir nigral cells. The correlation of motor deficits with the loss of TH-ir and DAT-ir nigral neurons suggests that aged nonhuman primates may provide a useful model for mimicking changes seen in human aging and early Parkinson's disease.

Journal ArticleDOI
TL;DR: The likelihood of a surviving infant resulting from pregnancy in dialysis patients is higher than previously observed and there is a suggestion that increased dialysis time may improve outcome.

Journal ArticleDOI
TL;DR: Rectal diazepam gel, administered at home by trained care givers, is an effective and well-tolerated treatment for acute repetitive seizures.
Abstract: Background Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. Methods We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at doses ranging from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses — one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. Results Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive s...

Journal ArticleDOI
TL;DR: In this paper, the authors examined the experience of spouses caregiving for their spouse with Parkinson's disease and to determine whether their experiences differed by stage of disease, using a cross-sectional design and mail questionnaire data from 380 spouse caregivers across 23 sites of the Parkinson Study Group.
Abstract: The objective of this study was to examine the experience of spouses caregiving for their spouse with Parkinson's disease (PD) and to determine whether their experiences differed by stage of disease. By using a cross-sectional design and mail questionnaire data from 380 spouse caregivers across 23 sites of the Parkinson Study Group, key caregiver variables were examined by stage of PD. Three categories of variables--caregiver role strain (10 measures), caregiver situation (four measures), and caregiver characteristics (four measures)--were analyzed by using t tests with Bonferroni correction. Specific types and amounts of role strain accumulated as the disease progressed, and they differed significantly between stages (p < 0.05). In the caregiving situation, the mean number of caregiving tasks tripled by stage 4/5. Negative changes in lifestyle plus decreases in predictability in caregivers' lives increased significantly in late-stage disease (p < 0.05). Caregiver characteristics of physical health and preparedness did not significantly differ across stages of disease. Depression was significantly higher by stage 4/5. Mutuality, the positive quality of the relationship as perceived by the caregiving spouse, declined beginning at stage 2. Caregiver strain is experienced across all stages of PD and accumulates significantly as the disease progresses. This study defines types and amounts of strain by stage of disease, which will be helpful in designing formal intervention trials to provide more effective help for spouse caregivers.

Journal ArticleDOI
TL;DR: A comprehensive review of the literature on repetition priming in normal aging and Alzheimer's disease is provided to articulate the issues that are critical to interpreting the empirical results, and discuss what new conclusions are suggested by the overall pattern of findings.
Abstract: On repetition priming tasks, memory is measured indirectly as a change in performance due to recent experience. It is often functionally and neurally dissociated from performance on explicit memory tasks, which directly measure conscious recall or recognition of recent events. Repetition priming has therefore been extensively studied in normal aging and Alzheimer's disease, which feature mild to severe changes in explicit memory. Initial studies indicated that repetition priming was immune to the effects of aging and greatly reduced in Alzheimer's disease (AD). As more studies have been performed, however, these initial conclusions appear less clear than before and, in the case of AD, actually misleading. The purpose of this article is to provide a comprehensive review of this rapidly expanding literature, articulate the issues that are critical to interpreting the empirical results, and discuss what new conclusions are suggested by the overall pattern of findings.

Journal ArticleDOI
TL;DR: In this paper, the Bone and Joint Decade 2000-2010 for prevention of musculo-skeletal disorders: Lund, Sweden, April 17-18, 1998, pp. 28-31.
Abstract: (1998). Epidemiology of low back pain. Acta Orthopaedica Scandinavica: Vol. 69, The Bone and Joint Decade 2000–2010 for prevention of musculo-skeletal disorders: Lund, Sweden, April 17–18, 1998, pp. 28-31.

Journal ArticleDOI
TL;DR: It is suggested that a Valsalva manoeuvre, blocking venous return through the superior vena cava, may allow brief retrograde transmission of high venous pressure from the arms to the cerebral venous system, resulting in venous ischaemia to the diencephalon or mesial temporal lobes and to TGA.

Journal ArticleDOI
TL;DR: In this paper, the authors compared the efficacy and safety of ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation in a multicenter study.