Impairment of bone turnover in elderly women with hip fracture

Summary Hip fracture is one of the most severe consequences of osteoporosis affecting aged women. However, abnormalities of bone turnover responsible for bone loss in this condition have not been clearly defined. To further evaluate the bone metabolic status of women sustaining hip fracture, we have prospectively measured serum osteocalcin as a marker of bone formation and urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-pyr) cross-links as markers of bone collagen degradation in 174 independently living women (80 ± 8 years) within a few hours after a hip fracture. Comparison was made with 77 age-matched controls (80 ± 5 years) and 17 premenopausal women (39 ± 3 years). In addition 15 of the patients were followed with daily measurements during the first postoperative week. At the time of admission osteocalcin was 20% lower in the fractured women compared to the elderly controls (7.6 ± 3.8 vs. 9.5 ± 4.5 nglml,P = 0.001). Pyr and D-pyr were 36% and 40% higher, respectively (P = 0.0001), than in elderly controls and 85% and 76% higher than in premenopausal controls (P = 0.0001). Serum osteocalcin did not correlate with the cortisol level measured at the same time (r = 0.03, ns), nor with serum albumin and creatinine. Serum osteocalcin remained unchanged within 18 hours after fracture, whereafter it progressively decreased until the third postoperative day. No correlation was noted between the excretion of pyridinoline cross-links and the time elapsed from fracture.These data suggest that the abnormal levels of osteocalcin and pyridinolines are unrelated to traumatically induced acute changes, but reflect abnormalities of bone turnover existing prior to the fracture. Thus, hip-fracture patients have biochemical evidence of decreased bone formation and increased bone resorption when compared to age-matched controls. We suggest that these abnormalities may play a role in the decrease of the bone mass and the consequently increased bone fragility that characterize the osteoporotic hip fracture in the elderly.     

中性粒细胞与淋巴细胞比值预测高龄卒中预后的价值

探讨中性粒细胞与淋巴细胞比值（NLR）对≥80岁急性缺血性脑卒中患者90 d预后的价值。方法 纳入2019年1月—2021年6月发病7 d内、≥80岁的缺血性卒中患者476例的相关信息、影像结果、随访结果,按照入组患者NLR的四分位数间距分为Q1组（NLR ＜2.97）、Q2组（ 2.97≤NLR ＜4.49）、Q3组（ 4.49≤NLR ＜7.94）、Q4组 （NLR≥7.94）,每组119例。根据不良结局发生率绘制K-M曲线,比较各组在不同时期的生存概率。采用Cox多因素回归分析影响患者不良预后的因素。结果log-rank检验显示,四组患者的生存率存在差异,Q4组的90 d生存率显著低于Q1组(P＜0.05)。多因素Cox回归分析显示,校正危险因素后,高NLR和高NIHSS评分是90 d死亡率的独立危险因素(P＜0.05)。根据ROC曲线,高NLR预测患者90 d死亡曲线下面积为0.74。结论 高NLR为影响≥80岁高龄急性缺血性卒中患者90 d预后的独立危险因素,对高龄急性缺血性脑卒中患者的90 d预后有预测价值     

Profile of etodolac: Pharmacokinetic evaluation in special populations

The pharmacokinetics of etodolac, a new nonsteroidal anti-inflammatory drug, were compared in normal subjects, in patients with renal and hepatic disease, and in elderly patients. In 28 normal subjects, orally administered etodolac was rapidly absorbed. By 1.2 hours after ingestion of a 200 mg dose, the maximum serum concentration (C_max) averaged 15.9 g/ml, with more than 99% of the drug bound to serum protein. Clearance was primarily hepatic. The mean half-life (t_1/2) was 6 to 7 hours. There were no apparent differences in C_max, the time at which C_max occurred (t_max), area under the serum concentration/time curve (AUC_0–24), or t_1/2 between groups of young men (n=20), elderly men (n=24), and elderly men with osteoarthritis (n=20), after a single dose of etodolac or after 7 days of subchronic administration. Moreover there was no evidence of accumulation. There also were no differences in C_max, t_max, AUC_0–24 or t_1/2 between groups of normal subjects (n=10) and patients with mild-to-moderate renal impairment (n=10). Patients with end-stage renal disease who were receiving chronic hemodialysis had the same mean serum concentration of free drug as normal subjects, even though mean serum levels of protein-bound etodolac were slightly lower than those in the normal subjects. The only significant (p<0.05) difference between patients with stable hepatic cirrhosis and normal, age-matched subjects was a slightly shorter t_max in the cirrhotic subjects (1.1 vs. 1.4 hours). These findings suggest that no alteration of etodolac dosage would be necessary in these high-risk groups.Die pharmakokinetischen Parameter von Etodolac, einem neuen, nichtsteroidalen entzündungshemmenden Therapeutikum, wurden an gesunden Probanden, an Patienten mit Leber- und Nierenleiden und an Älteren Patienten untersucht. Orale Etodolac Gaben wurden von den 28 gesunden Probanden schnell resorbiert. Nach einer einmaligen Dosis von 200 mg betrug nach 1,2 Stunden die durchschnittliche maximum Serumkonzentration (C_max) 15,9 g/ml, wobei mehr als 99% des Medikaments an das Serumprotein gebunden war. Clearance erfolgte hauptsÄchlich über die Niere. Die mittlere Eliminationshalbwertszeit (t_1/2) variierte zwischen 6 und 7 Stunden. In Bezug auf C_max, dem Zeitpunkt an dem C_max auftrat (t_max), FlÄche unter der Serumkonzentrationskurve (AUC_0–24) und t_1/2 wurden keine offensichtliche Unterschiede festgestellt zwischen der Gruppe junger MÄnnern (n=20), Älterer MÄnner (n=24) und Älteren MÄnnern mit Osteoarthritis (n=20) nach einer einmaligen Etodolac-Gabe oder nach 7 tÄgiger subchronischer Dosierung. Es bestanden auch keine Anzeichen einer Kumulation. ZusÄtzlich wurden auch keine Unterschiede in C_max, t_max, AUC_0–24 und t_1/2 zwischen der Gruppe gesunder Probanden (n=10) und der Patientengruppe mit leichten bis mÄigen NierenfunktionsschÄden (n=10) beobachtet. Im mittleren Serumspiegel des nicht gebundenen Medikaments in Patienten im Endstadium der Nierenerkrankung, die mit Langzeitdialyse behandelt wurden, konnte kein Unterschied im Vergleich zu gesunden Probanden festgestellt werden, obwohl der mittlere Serumspiegel für proteingebundenes Etodolac in den Patienten etwas niedriger lag als in gesunden Probanden. Der einzige signifikante Unterschied (p<0.05) zwischen Patienten mit stabilisierter Leberzirrhose und gleichaltrigen Probanden war eine etwas kürzere t_max in den Zirrhosepatienten (1,1 versus 1,4 Stunden). Diese Ergebnisse beweisen, dakeine Notwendigkeit vorliegt, die Etodolac-Dosierung für diese Risikogruppen zu modifizieren.Se comparó la farmacocinética de etodolac, un fármaco antiinflamatorio no esteroide nuevo, en sujetos normales y en pacientes con enfermedad renal y hepática y en pacientes ancianos. Etodolac administrado por vía oral a 28 sujetos normales fue rápidamente absorbido. A las 1,2 horas siguientes a la administración de una dosis de 200 mg, la concentración sérica máxima (C_max) alcanzó un promedio de 15,9 g/ml, con más del 99% del fármaco unido a la proteína sérica. La eliminación fue principalmente hepática. La vida media (t_1/2) fue 6–7 horas. No se observaron diferencias en C_max, en el tiempo en el cual se produjo C_max, en el área bajo la curva de concentración sérica/tiempo (ABC_0–24) ni en t_1/2 entre los grupos de hombres jóvenes (n=20), de hombres ancianos (n=24) y de hombres ancianos con osteoartritis (n=20), después de la administración de una dosis Única o después de 7 días de administración subcrónica de etodolac. Además, no hubo evidencia de acumulación. Tampoco se registraron diferencias en C_max, t_max, ABC_0–24 o t_1/2 entre los grupos de sujetos normales (n=10) y los pacientes con insuficiencia renal leve a moderada (n=10). Los pacientes con nefropatía terminal que estaban recibiendo hemodiálisis crónica tuvieron las mismas concentraciones séricas medias de fármaco libre que los sujetos normales, a pesar de que las concentraciones séricas medias de etodolac unido a proteina fueron levemente inferiores que en los sujetos normales. La Única diferencia significativa (p<0,05) entre los pacientes con cirrosis hepática estable y los sujetos normales de edad similar fue t_max ligeramente inferior en los sujetos cirróticos (1,1 vs 1,4 horas). Estos hallazgos sugieren que no es necesario modificar la dosis de etodolac para su uso en estos grupos de alto riesgo.La pharmacocinétique de l'étodolac, un anti-inflammatoire non stéroÏdien, a été comparé chez des sujets normaux et des patients présentant des affections rénales et hépatiques, et chez des malades âgés. Chez 28 sujets normaux, la résorption d'étodolac administré par voie orale a été rapide. Dès 1,2 heure suivant l'absorption d'une dose de 200 mg, la moyenne des concentration sériques maximales (C_max) était de 15,9 g/ml, plus de 99% pour cent du médicament étant liés aux protéines sériques. La clairance se fait surtout par voie hépatique. La demivie moyenne (t_1/2) était de 6 à 7 heures. Il n'y avait aucune différence apparente en ce qui concerne C_max, le temps d'apparition de C_max (t_max), l'aire sous la courbe concentration sérique/temps (AUC_0–24) ni t_1/2 entre les groupes d'hommes jeunes (n=20), d'hommes âgés (n=24), et d'hommes âgés atteints d'arthrose (n=20) à la suite d'une dose unique d'étodolac ou après 7 jours d'administration subchronique. De plus, aucune accumulation n'a été constatée. D'autre part, aucune différence de C_max, t_max, AUC_0–24 ni t_1/2 n'a été notée entre les groupes de sujets normaux (n=10) et de malades présentent des altérations rénales légères ou modérées (n=10). Les malades en insuffisance rénale terminale soumis à l'hémodialyse chronique ont présenté une concentration sérique moyenne de médicament libre analogue à celle des sujets normaux, mais la moyenne des taux sériques d'étodolac lié aux protéines était légèrement inférieure à celle observée chez les sujets normaux. La seule différence significative (p<0.05) entre les malades présentant une cirrhose hépatique stable et des sujets normaux appariés quant à l'âge était représentée par un t_max légèrement plus court chez les cirrhotiques (1,1 contre 1,4 heure). Ces données permettent de penser qu'aucune modification posologique de l'étodolac ne serait nécessaire pour ces groupes à haut risque.La farmacocinetica dell'etodolac, un nuovo farmaco anti-infiammatorio non steroidale è stata messa a confronto in gruppi normali, in pazienti affetti da malattia rénale ed epatica ed in pazienti anziani. In 28 soggetti normali l'etodolac somministrato oralmente è stato rapidamente assorbito. Dopo 1.2 ore dall'ingestione di una dose di 200 mg la massima concentrazione di siero (Cmax) presentava un valore medio di 15,9 mg/ml, con più del 99% del farmaco legato alla proteina del siero. La clearance era soprattutto a livello epatico. L'emivita media (t1/2) era di 6–7 ore. Non vi sono state evidenti differenze medie nei valori di concentrazione massima (Cmax), tempo (Tmax) al quale si aveva la Cmax, nella curva dell'area sotto concentrazione di siero/tempo (AUCo-24) oppure nel valore dell'emivita media (t1/2) tra gruppi di uomini giovani (n=20), uomini anziani (n=24) e anziani con osteoartrite (n=20), dopo una dose singola di etodolac o dopo 7 giorni di somministrazione subcronica. Inoltre non vi sono stati segni di accumulo. Per di più non vi sono state differenze nei valori di Cmax, tmax, AUCo-24 o t1/2 tra gruppi di soggetti normali (n=10) e pazienti con alterazioni renali da leggere a moderate (n=10). I pazienti con malattia renale all'ultimo stadio che ricevevano emodialisi cronica presentavano la stessa concentrazione media di siero di farmaco libero dei soggetti normali, anche se i livelli medi di siero di etodolac legato alle proteine erano leggermente inferiori a quelli di soggetti normali. L'unica differenza significativa (p<0.05) tra pazienti con cirrosi epatica stabile e soggetti normali della stessa età era nei tmax leggermente più brevi nei soggetti cirrotici (1.1. contro 1.4 ore). Questi risultati suggeriscono che nessuna alterazione del dosaggio di etodolac sarebbe necessaria in questi gruppi ad alto rischio.     

Papovavirus detection by electron microscopy in the brain of an elderly patient without overt progressive multifocal leukoencephalopathy

Virions resembling papovavirus were demonstrated in glial cells in the brain of an aged patient without overt progressive multifocal leukoencephalopathy. The patient was not in a severely immunocompromised state. On histological examination, only a few tiny incomplete necrotic foci were found in the subcortical area. These foci were widely dispersed. Rare, swollen oligodendroglial cells and astrocytes in which papovavirus capsid protein (VP-1) was demonstrated immunohistochemically were present around the foci. The two typical types of virus particles i.e. 35 to 40 nm round particles and elongated particles, were observed in the nuclei of the swollen glial cells. The latter were in the minority. Distinct crystals were also found in the nuclei. The centre-to-centre distance of the particles in the crystals, about 40 nm, and the electron-opaque spots of the round-shaped virions and of the elongated particles, were indicative of structural subunits of papovavirus capsids. This case provides further evidence that papovavirus, possibly JC virus, may be reactivated in the brains of aged patients who are not in an immunocompromised state.     

西酞普兰与马普替林治疗老年抑郁症的对照研究

目的探讨西酞普兰与马普替林治疗老年抑郁症的疗效和不良反应。方法将80例老年抑郁症患者随机分成两组，一组服用西酞普兰，另一组服用马普替林，疗程6周。采用汉密顿抑郁量表（HAMD）及药物副反应量表（TESS）定疗效和不良反应。结果西酞普兰组显效率为80％；马普替林组显效率为72．5％，两组差异无显著性。西酞普兰组不良反应较马普替林组少而轻。结论西酞普兰治疗老年抑郁症的疗效确切，起效快，不良反应轻，依从性好。     

Predicting pregnancy and spermatogenesis by survival analysis during gonadotrophin treatment of gonadotrophin-deficient infertile men

BACKGROUND: Predictors of fertility or spermatogenesis during gonadotrophin therapy of gonadotrophin-deficient men remain poorly defined. METHODS AND RESULTS: In order to evaluate potential predictors, this study evaluated 29 consecutive gonadotrophin-deficient men all desiring paternity who received 43 courses of therapy in one centre between 1982 and 1998. The Kaplan-Meier survival analysis estimates of median (SE) time to a sperm concentration of >0, >5 and >20 x 10(6)/ml were 5.5 (1.1), 12.4 (2.3) and 29.1 (1.9) months respectively. Conception occurred in 22/43 cycles (with eight men achieving two pregnancies) with a median (SE) Kaplan-Meier estimate of 20.5 (4.7) months. The median sperm concentration at conception was 5.0 (SE 2.0; range 0.0-59.5) x 10(6)/ml. Multivariate correlated Cox proportional hazards models predicting these same sperm thresholds and conception were developed by forward stepwise variable selection with verification of the model by backward stepping. Larger testicular volume, prior gonadotrophin therapy, completion of puberty, older age, the absence of adverse fertility factors and the absence of multiple pituitary hormone deficiency predicted a favourable response. Multivariate modelling suggests that the two most important predictors of sperm output are testicular volume and pubertal status. The most important potentially modifiable predictor was prior gonadotrophin therapy. The efficacy of recombinant and urinary FSH were similar. Prior androgen therapy and partner's age did not appear to be significant. CONCLUSIONS: Since prolonged treatment may be required to induce spermatogenesis, attention to these predictors may allow appropriate early use of advanced reproductive technologies.     

Round spermatids from infertile men exhibit decreased protamine-1 and -2 mRNA

During spermiogenesis, histone-to-protamine exchange causes chromatin condensation. Spermatozoa from infertile men are known to exhibit an increased protamine-1 (PRM1) to protamine-2 (PRM2) protein ratio. Since patients undergoing testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI) reveal low fertilization rates, whether the outcome of ICSI could be related to the percentage of round spermatids expressing PRM1-mRNA and PRM2-mRNA was investigated. Applying in-situ hybridization, 55 testicular biopsies from men undergoing TESE/ICSI were investigated. The percentage of PRM1-mRNA and PRM2-mRNA positive spermatids was significantly (P < 0.0001) decreased in men with at least qualitatively normal spermatogenesis (PRM1-mRNA: 58.4 +/- 13.8%; PRM2-mRNA: 56.4 +/- 11.3%) and impaired spermatogenesis (PRM1-mRNA: 32.6 +/- 10.8%; PRM2-mRNA: 31.7 +/- 11.1%) compared with men with obstructive azoospermia and quantitatively normal spermatogenesis (PRM1-mRNA: 79.9 +/- 4.6%; PRM2-mRNA: 78.1 +/- 5.7%). A positive correlation (r(PRM1) = 0.733; r(PRM2) = 0.784; P < 0.001) was demonstrated between the score and the percentage of PRM1-mRNA and PRM2-mRNA positive spermatids. While successful fertilization was neither related to the score, nor to the percentage of PRM1-mRNA and PRM2-mRNA positive spermatids, a significant (P < 0.05) relationship was demonstrated between successful fertilization and the PRM1-mRNA to PRM2-mRNA ratio. Therefore, the PRM1-mRNA to PRM2-mRNA ratio in round spermatids may serve as a possible predictive factor for the outcome of ICSI.     

腹膜透析治疗老年慢性肾功能衰竭的临床分析

目的 分析持续性腹膜透析(PD)治疗老年慢性肾功能衰竭(CRF)患者的临床效果,探讨PD在老年CRF患者中的应用经验.方法 回顾性分析89例老年CRF患者接受PD(简称老年PD组)治疗后的临床表现和生化指标、主要并发症、存活率、死亡原因等,并与53例非老年PD组相比较.结果 老年PD组的原发疾病以糖尿病(37.08%)、原发性高血压(30.34%)为主,而非老年PD组则以肾小球肾炎(54.72%)为主.两组患者的1年与3年存活率差异无统计学意义,腹膜炎仍是两组患者退出PD的主要原因.老年组的病死率明显高于非老年组,感染与心脑血管病是两组患者的主要并发症和死亡原因.低钾血症在老年PD患者中非常普遍.结论 腹膜透析在老年CRF患者的治疗中有效,但长期存活仍受腹膜炎、心脑血管病并发症的影响,老年PD患者的低钾血症应引起足够的重视.     

人工肱骨头置换与肱骨近端锁定钢板治疗老年复杂肱骨近端骨折的近期临床疗效分析

[摘要] 目的 对比分析人工肱骨头置换术和肱骨近端锁定钢板治疗老年复杂肱骨近端骨折的近期疗效。方法 回顾性分析本院骨科2012年1月~2014年6月采用人工肱骨头置换术和肱骨近端锁定钢板治疗的老年（年龄>65岁）NeerⅢ、Ⅳ部分肱骨近端骨折患者54例，人工肱骨头置换治疗（置换组）30例，肱骨近端锁定钢板内固定治疗（内固定组）24例。比较分析两组手术时间、术中出血量、随访Neer评分及Constant-Murley评分来评定两组临床疗效。结果 两组随访时间相仿，平均随访时间为19.5个月（12~36个月）。内固定组手术时间（101±13）分钟，术中出血量（237.9±32.4）mL，Neer评分（82.5±3.2），Constant-Murley评分（71.7±5.0）；置换组手术时间（98±11）分钟，术中出血量（246.0±39.8）mL，Neer评分（82.9±4.5），Constant-Murley评分（73.5±5.0）。两组手术时间、术中出血量、随访Neer及Constant-Murley评分比较差异均无统计学意义（P＞0.05）。内固定组有1例出现肩关节半脱位，肱骨头置换组有2例出现肩关节半脱位，通过三角巾悬吊后关节脱位均得到纠正。有1例四部分骨折患者，行内固定术后出现内固定松动、肱骨头坏死，改行人工肱骨头置换术。结论 人工肱骨头置换术和肱骨近端锁定钢板治疗老年肱骨近端复杂骨折的近期临床疗效相似，对不可修复的肱骨近端骨折宜行肱骨头置换术。