The identification of rare, large families with Parkinson's disease (PD) has provided important clues that have contributed to our understanding of this complex disorder. We have identified a large French-Canadian kindred that spans five generations consisting of more than 90 individuals. A total of 65 individuals now have been examined, had venous blood drawn, and DNA extracted. Two-point and multipoint linkage analysis was performed to assess linkage to known PD genes or loci. Within the third and fourth generations of this family there are 10 living, plus 3 deceased members with well-documented levodopa responsive parkinsonism. Autopsy results on 1 member demonstrated the loss of pigmented neurons in the substantia nigra and the presence of alpha-synuclein positive Lewy bodies. Four of the PD patients have prominent postural and kinetic tremors that preceded their parkinsonism by up to 10 years. Two other individuals within the family have prominent isolated postural and kinetic tremors without parkinsonism. The alpha-synuclein(4q21.3-23), Parkin(6q25.2-27), PARK3 (2p13), PARK4, and ubiquitin carboxy terminal hydrolase-L1 (4p14-16.3) and PARK6 and PARK7 (1p35-36) loci were excluded in this kindred using closely linked markers. The clinical and pathological features of this family are consistent with the diagnosis of PD. This family further demonstrates the known genetic heterogeneity in PD and is large enough that a genome-wide screen has been undertaken in an effort to identify a novel PD gene. 相似文献
Anxiety disorders are common in Parkinson's disease (PD). However, the risk of PD among people with anxiety has not been examined in a prospective cohort study. We examined this relation prospectively within the Health Professionals Follow-Up Study, a cohort of US male health professionals. In 1988, anxiety was assessed using the Crown-Crisp phobic anxiety index in 35,815 men without PD, stroke, or cancer at baseline. There were 189 incident cases of PD during 12 years of follow-up. After adjusting for age, smoking, and caffeine intake, the relative risk of PD among men with the highest level of anxiety (Crown-Crisp index scores of 4 and above) was 1.5 (95% CI = 1.0-2.1; P-trend = 0.01) compared to men with the lowest level of anxiety. This positive association persisted after excluding cases of PD with onset in the first 2 years of follow-up. Use of anxiolytic medication was also associated with an elevated risk of PD (RR= 1.6; 95% CI = 0.9-3.1), but adjusting for this potential confounder did not materially affect the association between anxiety and risk of PD. Our results suggest that anxiety is a risk factor for PD. Whether this association is causal or the result of shared underlying biology remains a question. 相似文献
Background. Partial harvesting of the left internal mammary artery (LIMA) is a widespread technique used during minimally invasive coronary operations performed through a left anterior small thoracotomy. The influence of persisting LIMA branches was investigated to evaluate their effect on the blood flow of the left anterior descending artery.
Methods. Thirty patients, 15 with totally (group A) and 15 with partially (group B) harvested LIMAs, were evaluated. All the patients underwent postoperative angiography, during which a flow map of the LIMA was performed. The average peak velocity and the diastolic-to-systolic peak velocity ratio were recorded. The LIMA graft flow pattern was recorded in the proximal and distal thirds of the artery. Intramammary adenosine (12 to 14 μg) was injected and the average peak velocities before and after injection were calculated.
Results. The average peak velocity was similar in both groups in the proximal and distal thirds of the LIMA (25 ± 7 and 26 ± 5 cm/sec, respectively, in group A versus 27 ± 5 and 25 ± 5 cm/sec, respectively in group B; p = NS). The diastolic-to-systolic peak velocity ratio was similar proximally (0.78 ± 0.3 in group A versus 0.69 ± 0.3 cm/s in group B; p = NS), but not distally (1.72 ± 0.1 in group A versus 0.97 ± 0.3 in group B; p < 0.0005). The LIMA graft flow reserve was similar both proximally and distally (2.6 ± 0.6 and 2.5 ± 0.3 cm/s, respectively, in group A versus 2.6 ± 0.5 and 2.6 ± 0.3 cm/s, respectively, in group B; p = NS).
Conclusions. The persistence of LIMA branches does not influence the blood flow of the left anterior descending artery after acute adenosine-induced myocardial hyperemia. If a left anterior small thoracotomy is used in left anterior descending artery direct revascularization, complete LIMA harvesting is not mandatory and depends on the personal preference of the surgeon. 相似文献
Axillary artery-to-coronary artery bypass using reversed saphenous vein provides a simple method of applying the minimally invasive coronary bypass grafting procedure when the internal thoracic artery is not an adequate conduit. Although this may allow extended use of the minimally invasive coronary bypass procedure, the long-term patency of this technique is unknown. 相似文献
Human osteoclasts are well characterized multinucleated cells whose function is the directed resorption of normal bone (NB).
Osteoclastic bone destruction accompanies lytic solid tumors and myeloma as well as Paget's disease (PD) of bone and giant
cell tumors of bone (GCTB). The mechanism of this stimulation of osteoclastic bone resorption is unknown. This study was designed
to detect cytokines present in the multinucleated cells of PD and GCTB in order to determine whether cytokine abnormalities
exist to account for bone lysis. Nine cytokines, representing the functions of bone resorption, angiogenesis, tumor necrosis,
bone cell proliferation, and osteoblast–osteoclast coupling, were examined by immunohistochemistry using tissue samples from
15 NB, 17 PD, and 19 GCTB patients. Standard nonparametric statistical analysis showed a significant increase (P < 0.01 to 0.05) in immunostaining between osteoclasts of PD and NB for interleukin-6 (Il-6), tumor necrosis factor beta (TNFβ),
epidermal growth factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). There was
a statistically significant decrease in immunostaining of giant cells of GCTB as compared with NB for transforming growth
factor beta (TGFβ), but no other differences from normal osteoclasts. The increase in staining of PD osteoclasts over the
giant cells of GCTB was significant (P < 0.01) for Il-6, TNFβ, PDGF, bFGF and insulin growth factor-1 (IGF-1), and (P < 0.05) for Il-1 and EGF. It was concluded that marked cytokine differences exist in vivo between osteoclasts of NB and PD lesions consistent with stimulated resorption. Alternatively, ``osteoclastoma' cells in
the center of the tumor did not overexpress the cytokines associated with bone lysis, suggesting some other mechanism for
stimulated resorption.
Received: 12 February 1996 / Accepted 31 December 1996 相似文献
A 65-year-old male patient with an 8-year history of poliostotic Paget’s disease complained of shoulder pain that started
6 months prior to admission. An extensive lytic area was identified in the right proximal humerus along with Paget’s disease.
There was cortical destruction and a soft tissue mass. Following an incisional biopsy, a diagnosis of grade 2 chondrosarcoma
associated with Paget’s disease was made. The histologic identification of chondrosarcoma associated with Paget’s disease
is rare. However, the presence of a calcified matrix in a destructive lesion associated with Paget’s disease should alert
the radiologist and the pathologist to the possibility of a chondromatous differentiation taking place in the sarcoma associated
with Paget’s disease. The histologic evaluation of the lesion will form the basis for the diagnosis. 相似文献