Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain

The effect of imipramine, desipramine, ketanserin and lithium on Type II glucocorticoid receptor (GR) mRNA levels was studied in rat brain regions involved in the control of the hypothalamo-pituitary-adrenal (HPA) axis, the dysregulation of which has been implicated in the pathophysiology of major depression. Northern blot analysis of Type II GR mRNA showed that treatment of male rats with either desipramine or imipramine increased hypothalamic and hippocampal GR mRNA levels. Upregulation of GR mRNA following administration of imipramine was found in brain regions of female rats, while desipramine had no effect. Ketanserin increased levels of GR mRNA in hippocampus of male, but not female, rats. Lithium also was able to induce important increases rat brain GR mRNA; this effect was particularly marked in females.

We conclude that desipramine, imipramine, ketanserin and lithium can modulate GR mRNA in regions of rat brain involved in the control of the HPA axis and may have a common mechanism of action at the level of the GR gene. Sexual dimorphism for drug regulation of brain GR mRNA content was shown and may be related to sex differences in the prevalence of certain affective disorders.     

Cemented and ingrowth fixation of the Miller-Galante prosthesis. Clinical and roentgenographic comparison after three- to six-year follow-up studies

One hundred thirty-nine cemented and 132 cementless Miller-Galante total knee prostheses were followed between three and six years (average, 43-44 months). The fixation technique was based on patient age, bone quality, and ability to delay full-weight bearing. Clinical follow-up studies were possible on 116 cemented knees. Fifteen knees were lost because of death before the three-year follow-up study, and eight knees required component removal. One hundred twenty-three cementless knees were available for clinical follow-up studies; there were three deaths, and six failures required component removal. No cemented failure was due to fixation, and three cementless failures were due to lack of tibial ingrowth in two and pain of undetermined etiology in one. Preoperative knee scores were slightly significant with cemented knees averaging 48 points and cementless knees averaging 52 points. A similar significant difference was maintained at the final follow-up study. No significant differences were noted for pain, limp, or support scores. Average range of motion was similar in the two groups. Radiolucent lines about the femoral component were rare. Cementless tibial radiolucencies were partial in up to 20% of examined zones, and complete tibial tray radiolucency was seen in only three patients. No correlation between radiolucency and knee scores was seen.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Measurement of bone by dual-photon absorptiometry (DPA) and dual-energy X-ray absorptiometry (DEXA)

Bone densitometry is essential for (a) confirming a diagnosis of osteoporosis, (b) determining the degree of osteopenia and risk of fracture, and (c) monitoring the response of bone to therapeutic agents. Fracture risk at specific axial fracture sites (spine, proximal femur), is associated directly with bone mineral density (BMD) at these sites. ROC analysis demonstrates that the diagnostic sensitivity of spine and femur BMD for spine and/or femur fracture is substantially superior to BMD of appendicular sites in the immediate postmenopausal period. Femoral neck BMD affords high diagnostic sensitivity for proximal femur fracture even in the elderly. Recent prospective studies have shown that bone densitometry can predict future fractures in postmenopausal women. Conventional DPA with 153Gd provides high accuracy for total body, spine, and femur BMD with adequate clinical precision of 1%, 2% and 3%, respectively. Dual-energy x-ray absorptiometry (DEXA), using either switched kVp or by k-edge filtering, offers better precision; typically the precision error is halved. The higher flux available from x-ray sources provides other advantages over DPA, including: improved spatial resolution (2 vs 4 mm), reduced radiation exposure (1 vs 2 mrem), and decreased scan times (3 to 10X). Improved DPA systems, with automatic gain stabilization to minimize drift, could offer clinical precision comparable to DEXA but the scan time and spatial resolution remain as before. Both DPA and DEXA allow detection of therapeutic efficacy in individual patients over the first year or two of therapy.     

Late side-effects with cosmetic relevance following soft X-ray therapy of cutaneous neoplasias

Background Cosmetic changes are to be expected after radiotherapy for skin tumours. Objectives This study aimed to answer the questions: How frequent are cosmetic changes after soft X‐ray therapy? Do treatment parameters, tumour thickness, localization and size of the irradiated field have a major influence? Were patients irritated by the visual appearance of the irradiated field? Methods In total, 2474 examinations of 1149 irradiated fields were performed. Results Hypopigmentation was found in 64.7% of examinations more than 90 days after therapy, teleangiectases in 43.1%, erythema in 24.8%, and hyperpigmentation in 16.8%. The frequency of hypopigmentation, teleangiectases and hyperpigmentation increased with time from X‐ray exposure; more than 4 years after therapy hypopigmentation was diagnosed in 91.8% and teleangiectases in 82.2% of examinations. Total dose, the time–dose–fractionation factor (TDF), field size and dose per fraction were significantly related to the frequency of cosmetic changes. Incidence rates of cosmetic changes differed by less than 15% if different treatment conditions were compared: thicker vs. thinner tumours, larger vs. smaller fields, higher vs. lower total doses, doses per fraction, and TDF. Frequencies of hypopigmentation, teleangiectases, erythema and hyperpigmentation differed by more than 15% between some localizations on the head. Women reported irritation by the visual appearance of the irradiated field in 12.6% of 1116 interviews, and men in 4.4% of 1284 interviews. Conclusions Cosmetic changes after soft X‐ray therapy are relatively frequent. Treatment parameters, tumour thickness and field size have only a minor influence. Few patients, but more women than men, were irritated by the visual appearance of the irradiated field.     

HYPOKALEMIA IN THE ELDERLY: IS IT ALWAYS DIURETIC-INDUCED?

SUMMARY Serum potassium was measured within 24 hours in 156 patients (48 male, 108 female) with an average age of 81.9 years admitted to the unit with acute illness. Of the 156 patients, 88 (56.4%) were taking diuretics (none was on ACE inhibitors); 20 patients (12.8%) were also on digoxin therapy. In all, 24 patients (16%) had hypokalaemia and 3 (2%) hyperkalaemia. Hypokalaemia was seen in patients associated with acute illness. There was no significant difference between the diuretic and non-diuretic groups. Monitoring of serum potassium is not routinely indicated to detect hypokalaemia in patients on diuretic therapy except in those with severe hepatic or renal impairment or those on digoxin.     

聚乙烯颗粒对人单核细胞分泌促炎因子与抗炎因子的影响

[目的]探讨聚乙烯颗粒对人单核细胞分泌促炎因子与抗炎因子的影响.[方法]用Ceridust 3615 颗粒(聚乙烯颗粒)(平均直径14.27,6.39,1.74,1.01,0.54和0.28 μm)分别刺激人单核细胞,颗粒体积与细胞数的比例为100:1和10:1.在颗粒刺激细胞24 h后,运用ELISA检测培养上清液中的促炎因子(白介素-1β,白介素-6和细胞坏死因子α)及抗炎因子(白介素-10)的表达.[结果]Ceridust 3615 颗粒可刺激单核细胞分泌白介素-1β(IL-1β)、白介素-6(IL-6)和细胞坏死因子α(TNFα),但未能引起白介素-10(IL-10)的表达.颗粒比例增高可促使单核细胞分泌更多的IL-6和TNFα,却减少IL-1β分泌,对IL-10的分泌则无影响.个体差异使巨噬细胞对同种颗粒的刺激产生不同的反应,其差异可达到30倍.[结论]个体差异是影响人工关节寿命的重要因素,聚乙烯颗粒可刺激单核细胞产生炎因子但对产生抗炎因子(IL-10)的作用不明显,提示促炎因子与抗炎因子的不平衡或许是人工关节松动不断进展的另一重要因素.