石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

The Increased Expression of Matrix Metalloproteinase-9 Messenger RNA in the Non-lesional Skin of Patients with Large Plaque Psoriasis Vulgaris

Background

A difference of the interleukin-18 (IL-18) mRNA expression among several proinflammatory genes was previously observed between large plaque (LP) psoriasis patients (more than 5 cm lesions are typical) and small plaque (SP) psoriasis patients (1~2 cm lesions are typical). Therefore, it is necessary to test whether there is any difference in the expression of the genes that activate IL-18 or the expression of genes that are induced by IL-18.

Objective

To test the differential mRNA expressions of caspase-1, STAT-6, MMP-1, MMP-2, MMP-9 and TIMP-1 according to the clinical types of psoriasis vulgaris lesions in Korean patients, we have analyzed the skin samples of psoriasis vulgaris patients.

Methods

The total cellular RNA of skin samples from groups of patient with LP and SP psoriasis was analyzed by performing real-time PCR (the Taqman method) to compare the differences in the mRNA expressions.

Results

The caspase-1 and STAT-6 mRNA expression levels from the SP lesional skin of the patients were increased compared with the caspase-1 and STAT-6 mRNA expression levels from SP non-lesional skin or normal skin, but these expression levels from the SP non-lesional skin were not significantly different from those of the LP non-lesional skin. Among MMP-1, MMP-2, MMP-9 and TIMP-1, the expressions of MMP-1, MMP-2 and MMP-9 mRNA were increased in the SP lesional skin compared with those of the SP non-lesional skin. The MMP-1 mRNA expressions in both the LP and SP lesional skin were increased compared with those in the normal skin (p=0.028 and p=0.007 respectively). The MMP-9 mRNA expression in the LP non-lesional skin was elevated compared with the MMP-9 mRNA expression in the SP non-lesional skin (p=0.047). The TIMP-1 mRNA expression levels from the non-lesional skin and the lesional skin of the psoriasis patients and the normal skin samples were not significantly different.

Conclusion

The increased expression of MMP-9 mRNA in the LP non-lesional skin compared to that of the SP non-lesional skin in the psoriatic skin suggests that the increased MMP-9 mRNA expression is related to the large size type of lesion.     

Knee mechanics after repair of the anterior cruciate ligament. A cadaver study of ligament augmentation

An experimental knee-testing system was used to investigate the immediate postoperative mechanical state in knees with nonaugmented and augmented repairs of the anterior cruciate ligament. Ligament, repair tissue, and augmentation forces were measured using buckle transducers, and joint motion was measured using an instrumented spatial linkage during the application of 90 N anteriorly-directed tibial loads to seven fresh knee specimens at 0-90 degrees of flexion. Force and motion data were collected from each knee with an intact and excised anterior cruciate ligament, and after performing (1) a nonaugmented repair and an augmented repair using the Ligament Augmentation Device (3M Company) placed either (2) anatomically through the lateral femoral condyle or (3) in the over-the-top position. The forces in the nonaugmented repair and the repair with the augmentation in the two positions were greater than the forces in the intact anterior cruciate ligament with the knee under the same anterior loads; this difference from normal was not significant with the over-the-top augmentation. With the augmentation anatomically placed, the load sharing did not reduce the force in the repair tissue as compared with the nonaugmented case. The over-the-top augmentation, on the other hand, lowered the repair tissue forces at extension while avoiding high repair tissue forces in flexion. The tibia was consistently in an externally rotated configuration compared with normal in both the unloaded and anterior load states with all three repair procedures.     

Physiologic categorization of asbestos-exposed workers

Categorization of the pattern of physiologic abnormalities in patients with asbestos-associated disease may be important for clinical, compensation, and epidemiologic reasons. A population of 658 asbestos-exposed workers was divided into six groups (restrictive, mixed restrictive-obstructive, obstructive, abnormal diffusing capacity, small airway disease, and normal) based upon pulmonary function test results. Use of two commonly employed prediction equations for diffusing capacity produced divergent results. Adjustment of the forced vital capacity for airtrapping based upon measurement of residual volume or of total lung capacity can improve the accuracy of categorization, particularly in smokers. Hence, the process of interpretation of pulmonary function testing should be chosen carefully.     

Association of hospital and surgeon volume of total hip replacement with functional status and satisfaction three years following surgery

OBJECTIVE: To evaluate whether hospital volume and surgeon volume of total hip replacements (THRs) are associated with patient-reported functional status and satisfaction with surgery 3 years postoperatively. METHODS: We performed a population-based cohort study of a stratified random sample of Medicare beneficiaries who underwent elective primary or revision THR in Ohio, Pennsylvania, or Colorado in 1995. The primary outcomes were the self-reported Harris hip score and a validated scale measuring satisfaction with the results of surgery. Both outcomes were assessed 3 years postoperatively. Hospital volume was defined as the aggregate number of elective primary and revision THRs performed on Medicare beneficiaries in the hospital in 1995. High-volume hospitals were defined as those in which >100 such procedures are performed annually, and low-volume centers were defined as those in which 12 procedures per year. CONCLUSION: Hospital volume and surgeon volume have little effect on 3-year functional outcome following THR, after adjusting for patient sociodemographic and select clinical characteristics. However, satisfaction with primary THR is greater among patients who underwent surgery in high-volume centers, and satisfaction with revisions is greater among patients whose operations were performed by higher-volume surgeons. Referring clinicians should incorporate these findings into their discussion of referral choices with patients considering THR. Conclusions regarding the effect of volume on longevity of the implants must await longer-term followup studies. Finally, further research is warranted to better understand the association between hospital and surgeon procedure volume and patient satisfaction with surgery.     

Anomalous origin of the left circumflex coronary artery from the right aortic sinus: A familial clustering

Origin of the left circumflex coronary artery from the right sinus of Valsalva or the right coronary artery is a well-described anomaly. We report 3 cases which suggest a familial association of this anomaly. The familial clustering that we report has not been previously demonstrated. © 1993 Wiley-Liss, Inc.     

Mummification of the infarcted myocardium by high dose corticosteroids

There is evidence that glucocorticoids reduce infarct size but their use in myocardial infarction remains controversial because of their potential adverse effects on healing of the infarct. To investigate the healing process, rats received either four parenteral doses of 50 mg/kg of methylprednisolone (MP) or saline 5 min, 3,6 and 24 hr after coronary occlusion and their hearts were examined by light and electron microscopy 48 hr and seven days after occlusion. At 48 hr, in five untreated rats, only 12 +/- 7% of injured myocytes showed the persistence of striations and a relatively intact sarcolemma despite loss of nuclei and hence appeared "mummified" whereas in six MP-treated rats 72 +/- 8% of myocytes exhibited this appearance (P less than 0.001). In treated rats there were fewer phagocytes than in controls. At seven days, in seven MP-rats, mummified cells were still more prominent than in five untreated rats and there were fewer phagocytes and less collagen. In conclusion, high dose of MP delays the inflammatory process and retards the disintegration of necrotic myocytes, resulting in impaired healing.